paxilline  (Alomone Labs)


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  • 94
    Name:
    Paxilline
    Description:
    Paxilline is a selective blocker of high conductance Ca2 activated Maxi K K channels
    Catalog Number:
    P-450
    Price:
    39.0
    Category:
    Small Molecule
    Source:
    Penicillium paxilli.
    Applications:
    0
    Purity:
    >98% (HPLC)
    Size:
    0 45 mg
    Format:
    Lyophilized/solid.
    Formula:
    C27H33NO4
    Molecular Weight:
    435.6
    Molecule Name:
    (2R,4bS,6aS,12bS,12cR,14aS)-5,6,6a,7,12,12b,12c,13,14,1 4a-Decahydro-4b-hydroxy-2-(1-hydroxy-1-methylethyl)-12b ,12c-dimethyl-2H-pyrano[2'',3'':5',6']benz[1',2':6,7]in deno[1,2-b]indol-3(4bH)-one.
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    Structured Review

    Alomone Labs paxilline
    Paxilline
    Paxilline is a selective blocker of high conductance Ca2 activated Maxi K K channels
    https://www.bioz.com/result/paxilline/product/Alomone Labs
    Average 94 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    paxilline - by Bioz Stars, 2021-09
    94/100 stars

    Images

    1) Product Images from "Blockade of BK channels attenuates chronic visceral hypersensitivity in an IBS-like rat model"

    Article Title: Blockade of BK channels attenuates chronic visceral hypersensitivity in an IBS-like rat model

    Journal: Molecular Pain

    doi: 10.1177/17448069211040364

    The RMP and EPSP of spinal cord lamina II neurons in IBS rats before and after the application of paxilline. (a) Representative action potential trace of an inhibitory interneuron. (b) Bar graph of the membrane potential of inhibitory neurons. Neurons, n = 11; animals, n = 9; ****: P
    Figure Legend Snippet: The RMP and EPSP of spinal cord lamina II neurons in IBS rats before and after the application of paxilline. (a) Representative action potential trace of an inhibitory interneuron. (b) Bar graph of the membrane potential of inhibitory neurons. Neurons, n = 11; animals, n = 9; ****: P

    Techniques Used:

    The sIPSCs and E/I of spinal cord lamina II neurons in IBS rats before and after application of paxilline. (a, b) Representative traces of sIPSC recorded from lamina II neurons in thoracolumbar spinal cord slices taken from IBS rats. (c, d) Bar graphs of the amplitude and frequency of sIPSCs in IBS rats. Neurons, n = 11; animals, n = 5 per group. (e) Representative traces of eEPSC (voltage clamped at −60 mv) and eIPSC (voltage clamped at 0 mv) recorded in the neuron of thoracolumbar spinal cord slice from IBS rats. The amplitude of eIPSCs increased after application of paxilline compared to the baseline. (f) Bar graph of the E/I ratio. Neurons, n = 8; animals, n = 5 per group; P = 0.0044. *: P
    Figure Legend Snippet: The sIPSCs and E/I of spinal cord lamina II neurons in IBS rats before and after application of paxilline. (a, b) Representative traces of sIPSC recorded from lamina II neurons in thoracolumbar spinal cord slices taken from IBS rats. (c, d) Bar graphs of the amplitude and frequency of sIPSCs in IBS rats. Neurons, n = 11; animals, n = 5 per group. (e) Representative traces of eEPSC (voltage clamped at −60 mv) and eIPSC (voltage clamped at 0 mv) recorded in the neuron of thoracolumbar spinal cord slice from IBS rats. The amplitude of eIPSCs increased after application of paxilline compared to the baseline. (f) Bar graph of the E/I ratio. Neurons, n = 8; animals, n = 5 per group; P = 0.0044. *: P

    Techniques Used:

    Effect of paxilline on rats. (a, b) Bar graphs of the EMG amplitude 30 min after spinal intrathecal injection of DMSO or paxilline (0.02, 0.2, 2, or 10 µM) with CRD at 40 mmHg or 60 mmHg in control rats, respectively; n = 6 per group. (c, d) Time curves of the effects of DMSO or paxilline (2 µM) at 40 and 60 mmHg CRD in control rats, respectively; n = 6 per group; *: P
    Figure Legend Snippet: Effect of paxilline on rats. (a, b) Bar graphs of the EMG amplitude 30 min after spinal intrathecal injection of DMSO or paxilline (0.02, 0.2, 2, or 10 µM) with CRD at 40 mmHg or 60 mmHg in control rats, respectively; n = 6 per group. (c, d) Time curves of the effects of DMSO or paxilline (2 µM) at 40 and 60 mmHg CRD in control rats, respectively; n = 6 per group; *: P

    Techniques Used: Injection

    2) Product Images from "Effective Activation of BKCa Channels by QO-40 (5-(Chloromethyl)-3-(Naphthalen-1-yl)-2-(Trifluoromethyl)Pyrazolo [1,5-a]pyrimidin-7(4H)-one), Known to Be an Opener of KCNQ2/Q3 Channels"

    Article Title: Effective Activation of BKCa Channels by QO-40 (5-(Chloromethyl)-3-(Naphthalen-1-yl)-2-(Trifluoromethyl)Pyrazolo [1,5-a]pyrimidin-7(4H)-one), Known to Be an Opener of KCNQ2/Q3 Channels

    Journal: Pharmaceuticals

    doi: 10.3390/ph14050388

    Stimulatory effect of QO-40 on the large-conductance Ca 2+ -activated K + (BK Ca ) channels identified in GH 3 cells. The single-channel experiments in an excised inside-out membrane patch were undertaken with symmetrical K + concentration (145 mM). The bath medium contained 0.1 μM Ca 2+ , and we kept the patch in voltage clamp at the level of +60 mV. ( A ) Representative current trace (upper, blue color) and the open probability (lower, red color) showing changes in the activity of BK Ca channels after addition of QO-40 (3 μM). Channel openings are indicated as upward deflections, and the horizontal bar shown above either current tracings or time course of single open probability corresponds to the application of QO-40 to the bath. The lower parts in ( A ) depict expanded records obtained from the dashed boxes in the uppermost part. Current traces in the left or right side indicate the absence or presence of 3 μM QO-40, respectively. Note that the presence of QO-40 leads to an increase in channel open-state probability of BK Ca channels. ( B ) BK Ca -channel activity obtained in the control period (i.e., neither QO-40 nor paxilline was present) (upper) and QO-40 (3 μM) plus paxilline (1 μM) (lower). In the experiments on QO-40 plus paxilline, paxilline (1 μM) was further added, as patch was continually exposed to QO-40 (3 μM). ( C ) Vertical scatter graph showing effects of QO-40, QO-40 plus TRAM-34, QO-40 plus linopirdine, or QO-40 plus paxilline on channel open-state probability of BK Ca channels (mean ± SEM; n = 8 for each point). Lino: 10 μM linopirdine; TRAM-34: 3 μM TRAM-34; Pax: 1 μM paxilline. Data analysis was performed by ANOVA-1 ( p
    Figure Legend Snippet: Stimulatory effect of QO-40 on the large-conductance Ca 2+ -activated K + (BK Ca ) channels identified in GH 3 cells. The single-channel experiments in an excised inside-out membrane patch were undertaken with symmetrical K + concentration (145 mM). The bath medium contained 0.1 μM Ca 2+ , and we kept the patch in voltage clamp at the level of +60 mV. ( A ) Representative current trace (upper, blue color) and the open probability (lower, red color) showing changes in the activity of BK Ca channels after addition of QO-40 (3 μM). Channel openings are indicated as upward deflections, and the horizontal bar shown above either current tracings or time course of single open probability corresponds to the application of QO-40 to the bath. The lower parts in ( A ) depict expanded records obtained from the dashed boxes in the uppermost part. Current traces in the left or right side indicate the absence or presence of 3 μM QO-40, respectively. Note that the presence of QO-40 leads to an increase in channel open-state probability of BK Ca channels. ( B ) BK Ca -channel activity obtained in the control period (i.e., neither QO-40 nor paxilline was present) (upper) and QO-40 (3 μM) plus paxilline (1 μM) (lower). In the experiments on QO-40 plus paxilline, paxilline (1 μM) was further added, as patch was continually exposed to QO-40 (3 μM). ( C ) Vertical scatter graph showing effects of QO-40, QO-40 plus TRAM-34, QO-40 plus linopirdine, or QO-40 plus paxilline on channel open-state probability of BK Ca channels (mean ± SEM; n = 8 for each point). Lino: 10 μM linopirdine; TRAM-34: 3 μM TRAM-34; Pax: 1 μM paxilline. Data analysis was performed by ANOVA-1 ( p

    Techniques Used: Concentration Assay, Activity Assay

    Effects of linopirdine, TRAM-34, GAL-021, and paxilline on QO-40-stimulated I K(Ca) in GH 3 cells. In this set of experiments, whole-cell current recordings were undertaken in cells bathed in normal Tyrode’s solution, and the pipet was backfilled with K + -containing internal solution. ( A ) Representative I K(Ca) traces in the absence (a, blue color) and presence of either QO-40 (b, red color), QO-40 plus linopirdine (c, upper panel, green color), or QO-40 plus paxilline (c, lower panel, brown color). The uppermost part shows the voltage-clamp protocol used. ( B ) Vertical scatter graph showing effects of linopirdine, TRAM-34, GAL-021, or paxilline on QO-40-induced stimulation of I K(Ca) (mean ± SEM; n = 6–8 for each point). QO-40: 3 μM QO-40; Lino: 10 μM linopirdine; TRAM-34: 3 μM TRAM-34; GAL-021: 3 μM GAL-021; Pax: 1 μM paxilline. Data analysis was performed by ANOVA-1 ( p
    Figure Legend Snippet: Effects of linopirdine, TRAM-34, GAL-021, and paxilline on QO-40-stimulated I K(Ca) in GH 3 cells. In this set of experiments, whole-cell current recordings were undertaken in cells bathed in normal Tyrode’s solution, and the pipet was backfilled with K + -containing internal solution. ( A ) Representative I K(Ca) traces in the absence (a, blue color) and presence of either QO-40 (b, red color), QO-40 plus linopirdine (c, upper panel, green color), or QO-40 plus paxilline (c, lower panel, brown color). The uppermost part shows the voltage-clamp protocol used. ( B ) Vertical scatter graph showing effects of linopirdine, TRAM-34, GAL-021, or paxilline on QO-40-induced stimulation of I K(Ca) (mean ± SEM; n = 6–8 for each point). QO-40: 3 μM QO-40; Lino: 10 μM linopirdine; TRAM-34: 3 μM TRAM-34; GAL-021: 3 μM GAL-021; Pax: 1 μM paxilline. Data analysis was performed by ANOVA-1 ( p

    Techniques Used:

    3) Product Images from "The quest for endothelial atypical cannabinoid receptor: BKCa channels act as cellular sensors for cannabinoids in in vitro and in situ endothelial cells"

    Article Title: The quest for endothelial atypical cannabinoid receptor: BKCa channels act as cellular sensors for cannabinoids in in vitro and in situ endothelial cells

    Journal: Vascular pharmacology

    doi: 10.1016/j.vph.2018.01.004

    Single channel activity of high conductance elicited by NAGly in patches excised from mice aortic endothelium. (A) Exemplary traces showing single channel activity recording from a patch excised from the endothelium of mouse aorta before (Control) and after exposure to 3 μM NAGly. Outside-out configuration. Bath and pipette solution contained 3 μM free Ca 2+ and 140 mM KCl. Vm = +40 mV. (B) Current traces elicited by voltage ramps from − 100 to 100 mV in outside-out patch excised from mouse aortic endothelium and exposed to 3 μM NAGly. (C) Single channel activity from a patch excided from the endothelium of a NAGly-pre-treated strip at physiological voltages (− 40 mV and − 60 mV) and in the presence of 3 μM free Ca 2+ . Channel openings are shown as downward deflections. (D) Single channel activity from inside-out patch excised from the endothelium of NAGly (3 μM)-pretreated aortic strip before (control) and after exposure to paxilline (2 μM, n = 3). Vm = +60 mV, 3 μM free Ca 2+ .
    Figure Legend Snippet: Single channel activity of high conductance elicited by NAGly in patches excised from mice aortic endothelium. (A) Exemplary traces showing single channel activity recording from a patch excised from the endothelium of mouse aorta before (Control) and after exposure to 3 μM NAGly. Outside-out configuration. Bath and pipette solution contained 3 μM free Ca 2+ and 140 mM KCl. Vm = +40 mV. (B) Current traces elicited by voltage ramps from − 100 to 100 mV in outside-out patch excised from mouse aortic endothelium and exposed to 3 μM NAGly. (C) Single channel activity from a patch excided from the endothelium of a NAGly-pre-treated strip at physiological voltages (− 40 mV and − 60 mV) and in the presence of 3 μM free Ca 2+ . Channel openings are shown as downward deflections. (D) Single channel activity from inside-out patch excised from the endothelium of NAGly (3 μM)-pretreated aortic strip before (control) and after exposure to paxilline (2 μM, n = 3). Vm = +60 mV, 3 μM free Ca 2+ .

    Techniques Used: Activity Assay, Mouse Assay, Transferring, Stripping Membranes

    NAGly and abn-cbd induce BK ca -dependent endothelial cell hyperpolarization in mouse aorta independently of gap junctions and GPR18. (A) A lack of effect of phenylephrine (1 μM) on the membrane potential of endothelial cells in isolated mouse aorta. Note that subsequent administration of Ach produces a hyperpolarization. (B) In the endothelium of isolated rat aorta, phenylephrine produces depolarization with membrane potential oscillations. (C) Effect of 10 μM NAGly (n = 5) on endothelial membrane potential in isolated mouse aorta. (D) Effect of 30 μM NAGly on endothelial membrane potential in isolated mouse aorta (n = 4). (E) Membrane potential recording showing the effect of paxilline (1 μM) on the hyperpolarization induced by NAGly (n = 3). (F) Membrane potential recording showing a failure of TRAM-34 to suppress the hyperpolarization to 10 μM abn-cbd in excised mouse aorta. (G) Intracellular perfusion with GPR18 antibody (1:500) fails to prevent endothelial cell hyperpolarization to 10 μM NAGly in isolated mouse aorta (n = 4). Recordings were commenced in the presence of 100 μM glycyrrhetinic acid, a gap junction inhibitor. (H) Bars showing the magnitude of shifts in endothelial membrane potential in isolated mice aorta induced by NAGly (10 μM and 30 μM) alone and combination of 10 μM NAGly and paxilline (1 μM) and GPR18 antibody. (I) Effect of NS1619 on the membrane potential of endothelial cells in excised mouse aorta. (J) Bars showing mean values of endothelial cell hyperpolarization to 10 μM (n = 6) and 30 μM NS1619 (n = 5).
    Figure Legend Snippet: NAGly and abn-cbd induce BK ca -dependent endothelial cell hyperpolarization in mouse aorta independently of gap junctions and GPR18. (A) A lack of effect of phenylephrine (1 μM) on the membrane potential of endothelial cells in isolated mouse aorta. Note that subsequent administration of Ach produces a hyperpolarization. (B) In the endothelium of isolated rat aorta, phenylephrine produces depolarization with membrane potential oscillations. (C) Effect of 10 μM NAGly (n = 5) on endothelial membrane potential in isolated mouse aorta. (D) Effect of 30 μM NAGly on endothelial membrane potential in isolated mouse aorta (n = 4). (E) Membrane potential recording showing the effect of paxilline (1 μM) on the hyperpolarization induced by NAGly (n = 3). (F) Membrane potential recording showing a failure of TRAM-34 to suppress the hyperpolarization to 10 μM abn-cbd in excised mouse aorta. (G) Intracellular perfusion with GPR18 antibody (1:500) fails to prevent endothelial cell hyperpolarization to 10 μM NAGly in isolated mouse aorta (n = 4). Recordings were commenced in the presence of 100 μM glycyrrhetinic acid, a gap junction inhibitor. (H) Bars showing the magnitude of shifts in endothelial membrane potential in isolated mice aorta induced by NAGly (10 μM and 30 μM) alone and combination of 10 μM NAGly and paxilline (1 μM) and GPR18 antibody. (I) Effect of NS1619 on the membrane potential of endothelial cells in excised mouse aorta. (J) Bars showing mean values of endothelial cell hyperpolarization to 10 μM (n = 6) and 30 μM NS1619 (n = 5).

    Techniques Used: Isolation, Mouse Assay

    4) Product Images from "The quest for endothelial atypical cannabinoid receptor: BKCa channels act as cellular sensors for cannabinoids in in vitro and in situ endothelial cells"

    Article Title: The quest for endothelial atypical cannabinoid receptor: BKCa channels act as cellular sensors for cannabinoids in in vitro and in situ endothelial cells

    Journal: Vascular pharmacology

    doi: 10.1016/j.vph.2018.01.004

    Single channel activity of high conductance elicited by NAGly in patches excised from mice aortic endothelium. (A) Exemplary traces showing single channel activity recording from a patch excised from the endothelium of mouse aorta before (Control) and after exposure to 3 μM NAGly. Outside-out configuration. Bath and pipette solution contained 3 μM free Ca 2+ and 140 mM KCl. Vm = +40 mV. (B) Current traces elicited by voltage ramps from − 100 to 100 mV in outside-out patch excised from mouse aortic endothelium and exposed to 3 μM NAGly. (C) Single channel activity from a patch excided from the endothelium of a NAGly-pre-treated strip at physiological voltages (− 40 mV and − 60 mV) and in the presence of 3 μM free Ca 2+ . Channel openings are shown as downward deflections. (D) Single channel activity from inside-out patch excised from the endothelium of NAGly (3 μM)-pretreated aortic strip before (control) and after exposure to paxilline (2 μM, n = 3). Vm = +60 mV, 3 μM free Ca 2+ .
    Figure Legend Snippet: Single channel activity of high conductance elicited by NAGly in patches excised from mice aortic endothelium. (A) Exemplary traces showing single channel activity recording from a patch excised from the endothelium of mouse aorta before (Control) and after exposure to 3 μM NAGly. Outside-out configuration. Bath and pipette solution contained 3 μM free Ca 2+ and 140 mM KCl. Vm = +40 mV. (B) Current traces elicited by voltage ramps from − 100 to 100 mV in outside-out patch excised from mouse aortic endothelium and exposed to 3 μM NAGly. (C) Single channel activity from a patch excided from the endothelium of a NAGly-pre-treated strip at physiological voltages (− 40 mV and − 60 mV) and in the presence of 3 μM free Ca 2+ . Channel openings are shown as downward deflections. (D) Single channel activity from inside-out patch excised from the endothelium of NAGly (3 μM)-pretreated aortic strip before (control) and after exposure to paxilline (2 μM, n = 3). Vm = +60 mV, 3 μM free Ca 2+ .

    Techniques Used: Activity Assay, Mouse Assay, Transferring, Stripping Membranes

    NAGly and abn-cbd induce BK ca -dependent endothelial cell hyperpolarization in mouse aorta independently of gap junctions and GPR18. (A) A lack of effect of phenylephrine (1 μM) on the membrane potential of endothelial cells in isolated mouse aorta. Note that subsequent administration of Ach produces a hyperpolarization. (B) In the endothelium of isolated rat aorta, phenylephrine produces depolarization with membrane potential oscillations. (C) Effect of 10 μM NAGly (n = 5) on endothelial membrane potential in isolated mouse aorta. (D) Effect of 30 μM NAGly on endothelial membrane potential in isolated mouse aorta (n = 4). (E) Membrane potential recording showing the effect of paxilline (1 μM) on the hyperpolarization induced by NAGly (n = 3). (F) Membrane potential recording showing a failure of TRAM-34 to suppress the hyperpolarization to 10 μM abn-cbd in excised mouse aorta. (G) Intracellular perfusion with GPR18 antibody (1:500) fails to prevent endothelial cell hyperpolarization to 10 μM NAGly in isolated mouse aorta (n = 4). Recordings were commenced in the presence of 100 μM glycyrrhetinic acid, a gap junction inhibitor. (H) Bars showing the magnitude of shifts in endothelial membrane potential in isolated mice aorta induced by NAGly (10 μM and 30 μM) alone and combination of 10 μM NAGly and paxilline (1 μM) and GPR18 antibody. (I) Effect of NS1619 on the membrane potential of endothelial cells in excised mouse aorta. (J) Bars showing mean values of endothelial cell hyperpolarization to 10 μM (n = 6) and 30 μM NS1619 (n = 5).
    Figure Legend Snippet: NAGly and abn-cbd induce BK ca -dependent endothelial cell hyperpolarization in mouse aorta independently of gap junctions and GPR18. (A) A lack of effect of phenylephrine (1 μM) on the membrane potential of endothelial cells in isolated mouse aorta. Note that subsequent administration of Ach produces a hyperpolarization. (B) In the endothelium of isolated rat aorta, phenylephrine produces depolarization with membrane potential oscillations. (C) Effect of 10 μM NAGly (n = 5) on endothelial membrane potential in isolated mouse aorta. (D) Effect of 30 μM NAGly on endothelial membrane potential in isolated mouse aorta (n = 4). (E) Membrane potential recording showing the effect of paxilline (1 μM) on the hyperpolarization induced by NAGly (n = 3). (F) Membrane potential recording showing a failure of TRAM-34 to suppress the hyperpolarization to 10 μM abn-cbd in excised mouse aorta. (G) Intracellular perfusion with GPR18 antibody (1:500) fails to prevent endothelial cell hyperpolarization to 10 μM NAGly in isolated mouse aorta (n = 4). Recordings were commenced in the presence of 100 μM glycyrrhetinic acid, a gap junction inhibitor. (H) Bars showing the magnitude of shifts in endothelial membrane potential in isolated mice aorta induced by NAGly (10 μM and 30 μM) alone and combination of 10 μM NAGly and paxilline (1 μM) and GPR18 antibody. (I) Effect of NS1619 on the membrane potential of endothelial cells in excised mouse aorta. (J) Bars showing mean values of endothelial cell hyperpolarization to 10 μM (n = 6) and 30 μM NS1619 (n = 5).

    Techniques Used: Isolation, Mouse Assay

    5) Product Images from "A junctophilin-caveolin interaction enables efficient coupling between ryanodine receptors and BKCa channels in the Ca2+ microdomain of vascular smooth muscle"

    Article Title: A junctophilin-caveolin interaction enables efficient coupling between ryanodine receptors and BKCa channels in the Ca2+ microdomain of vascular smooth muscle

    Journal: The Journal of Biological Chemistry

    doi: 10.1074/jbc.RA119.008342

    JP2 facilitates the efficiency of STOCs in mMASMCs. A, STOCs were recorded in siControl and siJP2-treated myocytes at a holding potential of −20 mV. STOCs were completely blocked by 1 μ m paxilline ( Pax ). B, distribution histogram of STOC events versus their peak amplitude. C–E, summary of the mean STOC amplitude, frequency and integral for 30 s in myocytes treated with siControl (9 cells from 6 mice) or siJP2 (8 cells from 7 mice). F, images of vasocontractions caused by 1 μ m Pax. The averaged diameter (μm) for: siControl, 125.7 ± 9.2 (Control) and 116.8 ± 10.0 (1 μ m Pax); siJP2, 133.5 ± 14.6 (Control) and 130.5 ± 13.1 (1 μ m Pax). G, summarized data of 1 μ m Pax-induced decreases in the diameter of mesenteric arteries treated with siControl ( n = 4 from 3 mice) and siJP2 ( n = 4 from 3 mice). *, p
    Figure Legend Snippet: JP2 facilitates the efficiency of STOCs in mMASMCs. A, STOCs were recorded in siControl and siJP2-treated myocytes at a holding potential of −20 mV. STOCs were completely blocked by 1 μ m paxilline ( Pax ). B, distribution histogram of STOC events versus their peak amplitude. C–E, summary of the mean STOC amplitude, frequency and integral for 30 s in myocytes treated with siControl (9 cells from 6 mice) or siJP2 (8 cells from 7 mice). F, images of vasocontractions caused by 1 μ m Pax. The averaged diameter (μm) for: siControl, 125.7 ± 9.2 (Control) and 116.8 ± 10.0 (1 μ m Pax); siJP2, 133.5 ± 14.6 (Control) and 130.5 ± 13.1 (1 μ m Pax). G, summarized data of 1 μ m Pax-induced decreases in the diameter of mesenteric arteries treated with siControl ( n = 4 from 3 mice) and siJP2 ( n = 4 from 3 mice). *, p

    Techniques Used: Mouse Assay

    6) Product Images from "GPR55 agonist lysophosphatidylinositol and lysophosphatidylcholine inhibit endothelial cell hyperpolarization via GPR-independent suppression of Na+-Ca2+ exchanger and endoplasmic reticulum Ca2+ refilling"

    Article Title: GPR55 agonist lysophosphatidylinositol and lysophosphatidylcholine inhibit endothelial cell hyperpolarization via GPR-independent suppression of Na+-Ca2+ exchanger and endoplasmic reticulum Ca2+ refilling

    Journal: Vascular pharmacology

    doi: 10.1016/j.vph.2017.01.002

    LPC16:0 produces hyperpolarization of EA.hy926 cells and activation of BK Ca channels independently G-protein coupled receptors. (A) Membrane potential recording showing the effect of 3 μM LPC16:0 on the membrane potential of EA.hy926 cells. (B) Representative whole-cell K + currents in response to voltage ramps from −80 to +80 mV in the absence (control), and presence of 3 μM LPC16:0 and in the combined presence of 3 μM LPC16:0 and 1 μM paxilline. Exemplary record out of 5 individual experiments.
    Figure Legend Snippet: LPC16:0 produces hyperpolarization of EA.hy926 cells and activation of BK Ca channels independently G-protein coupled receptors. (A) Membrane potential recording showing the effect of 3 μM LPC16:0 on the membrane potential of EA.hy926 cells. (B) Representative whole-cell K + currents in response to voltage ramps from −80 to +80 mV in the absence (control), and presence of 3 μM LPC16:0 and in the combined presence of 3 μM LPC16:0 and 1 μM paxilline. Exemplary record out of 5 individual experiments.

    Techniques Used: Activation Assay

    7) Product Images from "Large-conductance calcium-activated potassium current modulates excitability in isolated canine intracardiac neurons"

    Article Title: Large-conductance calcium-activated potassium current modulates excitability in isolated canine intracardiac neurons

    Journal: American Journal of Physiology - Cell Physiology

    doi: 10.1152/ajpcell.00148.2012

    Fast-activated outward current component from canine IC neurons is sensitive to tetraethylammonium (TEA). A : representative traces of paxilline and TEA-sensitive outward currents elicited by 250 ms voltage steps from −50 to 10 mV, from a holding
    Figure Legend Snippet: Fast-activated outward current component from canine IC neurons is sensitive to tetraethylammonium (TEA). A : representative traces of paxilline and TEA-sensitive outward currents elicited by 250 ms voltage steps from −50 to 10 mV, from a holding

    Techniques Used: Mass Spectrometry

    8) Product Images from "Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin–Darby canine kidney cells"

    Article Title: Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin–Darby canine kidney cells

    Journal: Toxicology Reports

    doi: 10.1016/j.toxrep.2015.08.010

    Effect of Iban on I K recorded from MDCK cells. (A) Original current traces obtained with or without addition of Iban at −50 mV and a long ramp pulse from−100 to +60 mV with a duration of 1 s at a rate of 0.05 Hz. a: control (black); b: 10 μM Iban (blue); c: 30 μM Iban (red). (B) Summary of the data showing effects of Iban, paxilline, ketamine and Iban plus NaHS on the I K amplitude measured at the level of +40 mV. Values are means ± SEM for n = 15–18 cells for each group. Iban: 30 μM Iban; Pax: 1 μM paxilline; Ketamine: 100 μM ketamine; NaHS: 100 μM sodium hydrosulfide. * Significantly different from control ( P
    Figure Legend Snippet: Effect of Iban on I K recorded from MDCK cells. (A) Original current traces obtained with or without addition of Iban at −50 mV and a long ramp pulse from−100 to +60 mV with a duration of 1 s at a rate of 0.05 Hz. a: control (black); b: 10 μM Iban (blue); c: 30 μM Iban (red). (B) Summary of the data showing effects of Iban, paxilline, ketamine and Iban plus NaHS on the I K amplitude measured at the level of +40 mV. Values are means ± SEM for n = 15–18 cells for each group. Iban: 30 μM Iban; Pax: 1 μM paxilline; Ketamine: 100 μM ketamine; NaHS: 100 μM sodium hydrosulfide. * Significantly different from control ( P

    Techniques Used:

    9) Product Images from "Glutamate-activated BK channel complexes formed with NMDA receptors"

    Article Title: Glutamate-activated BK channel complexes formed with NMDA receptors

    Journal: Proceedings of the National Academy of Sciences of the United States of America

    doi: 10.1073/pnas.1802567115

    Postsynaptic BK channels regulate synaptic transmission in mature dentate granule cells via NMDAR-mediated channel activation. ( A ) Effects of paxilline (Pax) alone and combined with AP5 on the amplitudes of evoked EPSPs ( n = 13). ( B ) Effects of AP5 alone and combined with paxilline on the amplitudes of evoked EPSPs ( n = 13). For comparison, the effects of AP5 alone on evoked EPSPs over a similar extended time course ( n = 6) were included in the averaged plot. ( C ) Effects of paxilline alone and combined with AP5 on the amplitudes of evoked EPSPs in mature granule cells in BKα-KO (Nestin-Cre + /KCNMA1 fl/fl ) mice ( n = 9). ( D ) The effect of paxilline alone (bath) and combined with AP5 (bath) on evoked EPSPs in the presence of intracellularly applied MK-801 ( n = 9). ( E ) Effects of paxilline on evoked EPSPs in the presence of intracellularly applied paxilline ( n = 8). ( F ) Effects of paxilline on evoked EPSPs in the presence of intracellularly applied 0.5 mg/mL BKα46–93 ( n = 8) or scrambled ( n = 7) peptide. Pep., peptide. ( G ) Effects of extracellularly and intracellularly applied paxilline ( n = 9 and 7, respectively) and KO of BK channels (Nestin-Cre + /KCNMA1 fl/fl ) ( n = 5) on paired-pulse ratios. All experiments were done with regular C57BL/C6 mice except as specified. Control, data obtained without or before drug application. Paxilline and AP5 were perfused in the bath solution at a concentration of 10 and 200 µM, respectively, and they were applied either individually or combined together at a later stage of the experiment. Statistical differences were evaluated by using a t test. N.S., not significant. * P
    Figure Legend Snippet: Postsynaptic BK channels regulate synaptic transmission in mature dentate granule cells via NMDAR-mediated channel activation. ( A ) Effects of paxilline (Pax) alone and combined with AP5 on the amplitudes of evoked EPSPs ( n = 13). ( B ) Effects of AP5 alone and combined with paxilline on the amplitudes of evoked EPSPs ( n = 13). For comparison, the effects of AP5 alone on evoked EPSPs over a similar extended time course ( n = 6) were included in the averaged plot. ( C ) Effects of paxilline alone and combined with AP5 on the amplitudes of evoked EPSPs in mature granule cells in BKα-KO (Nestin-Cre + /KCNMA1 fl/fl ) mice ( n = 9). ( D ) The effect of paxilline alone (bath) and combined with AP5 (bath) on evoked EPSPs in the presence of intracellularly applied MK-801 ( n = 9). ( E ) Effects of paxilline on evoked EPSPs in the presence of intracellularly applied paxilline ( n = 8). ( F ) Effects of paxilline on evoked EPSPs in the presence of intracellularly applied 0.5 mg/mL BKα46–93 ( n = 8) or scrambled ( n = 7) peptide. Pep., peptide. ( G ) Effects of extracellularly and intracellularly applied paxilline ( n = 9 and 7, respectively) and KO of BK channels (Nestin-Cre + /KCNMA1 fl/fl ) ( n = 5) on paired-pulse ratios. All experiments were done with regular C57BL/C6 mice except as specified. Control, data obtained without or before drug application. Paxilline and AP5 were perfused in the bath solution at a concentration of 10 and 200 µM, respectively, and they were applied either individually or combined together at a later stage of the experiment. Statistical differences were evaluated by using a t test. N.S., not significant. * P

    Techniques Used: Transmission Assay, Activation Assay, Mouse Assay, Concentration Assay

    Glutamate-induced BK channel activation via NMDARs in mature dentate gyrus granule cells. ( A ) Whole-cell recording of glutamate-induced currents at different holding membrane voltages upon somatic puff application of 100 μM glutamate and 10 μM glycine for 100 ms. ( B ) Representative glutamate-induced currents at −10 mV in the absence and presence of the BK channel blocker paxilline (Pax; 10 μM) and NMDAR antagonist AP5 (200 μM) and in the presence of the intracellular chelators EGTA and BAPTA. ( C ) Averaged effects of paxilline ( n = 13), AP5 ( n = 13), and intracellular chelators (0.2 mM EGTA, n = 26; 2 mM EGTA, n = 8; 2 mM BAPTA, n = 8) on the glutamate-induced outward currents. ( D ) Representative glutamate-induced currents at −10 mV with recording pipette solution containing 0.5 mg/mL BKα46–93 peptide or scrambled peptide and the bath solution perfused with/without AP5 (200 μM). Pep., peptide. ( E ) Averaged amplitudes of glutamate-induced outward currents in the presence of the intracellularly loaded BKα46–93 ( n = 9) or scrambled ( n = 8) peptide. The current amplitudes were calculated from the peak amplitudes of outward currents relative to the current levels before drug application. Data are shown as means ± SEM. Statistical differences were evaluated using a t test. N.S., not significant. * P
    Figure Legend Snippet: Glutamate-induced BK channel activation via NMDARs in mature dentate gyrus granule cells. ( A ) Whole-cell recording of glutamate-induced currents at different holding membrane voltages upon somatic puff application of 100 μM glutamate and 10 μM glycine for 100 ms. ( B ) Representative glutamate-induced currents at −10 mV in the absence and presence of the BK channel blocker paxilline (Pax; 10 μM) and NMDAR antagonist AP5 (200 μM) and in the presence of the intracellular chelators EGTA and BAPTA. ( C ) Averaged effects of paxilline ( n = 13), AP5 ( n = 13), and intracellular chelators (0.2 mM EGTA, n = 26; 2 mM EGTA, n = 8; 2 mM BAPTA, n = 8) on the glutamate-induced outward currents. ( D ) Representative glutamate-induced currents at −10 mV with recording pipette solution containing 0.5 mg/mL BKα46–93 peptide or scrambled peptide and the bath solution perfused with/without AP5 (200 μM). Pep., peptide. ( E ) Averaged amplitudes of glutamate-induced outward currents in the presence of the intracellularly loaded BKα46–93 ( n = 9) or scrambled ( n = 8) peptide. The current amplitudes were calculated from the peak amplitudes of outward currents relative to the current levels before drug application. Data are shown as means ± SEM. Statistical differences were evaluated using a t test. N.S., not significant. * P

    Techniques Used: Activation Assay, Mass Spectrometry, Transferring

    10) Product Images from "A Role for BK Channels in Heart Rate Regulation in Rodents"

    Article Title: A Role for BK Channels in Heart Rate Regulation in Rodents

    Journal: PLoS ONE

    doi: 10.1371/journal.pone.0008698

    The effects of lolitrem B and paxilline on blood pressure and heart rate in Kcnma1 −/− mice and wild-type littermates. Inhibitors were added immediately after the control reading at time zero as indicated by the arrow. Mean blood pressure following treatment with (A) 4 mg/kg lolitrem B, or (B) 8 mg/kg paxilline. Heart rate following treatment with (C) lolitrem B, or (D) paxilline. Data are mean ± S.E.M. for n = 4 in each treatment group. Significance was tested using Tukey-Kramer post hoc test after a repeated measures analysis of variance. Asterisks indicate the significance of each treatment in wild-type mice compared with the pre-drug control at time = 0. *, P
    Figure Legend Snippet: The effects of lolitrem B and paxilline on blood pressure and heart rate in Kcnma1 −/− mice and wild-type littermates. Inhibitors were added immediately after the control reading at time zero as indicated by the arrow. Mean blood pressure following treatment with (A) 4 mg/kg lolitrem B, or (B) 8 mg/kg paxilline. Heart rate following treatment with (C) lolitrem B, or (D) paxilline. Data are mean ± S.E.M. for n = 4 in each treatment group. Significance was tested using Tukey-Kramer post hoc test after a repeated measures analysis of variance. Asterisks indicate the significance of each treatment in wild-type mice compared with the pre-drug control at time = 0. *, P

    Techniques Used: Mouse Assay

    The effect of paxilline and iberiotoxin on heart rate in the isolated rat heart. (A) 1 µM paxilline (Pax) was added at time = 40 min and infused for 10 min, preceded by a control infusion of Krebs-Henseleit perfusion fluid with 0.1% DMSO ( n = 5). (B) Heart rate before, during and after infusion at time zero of different concentrations of paxilline (1, 5 or 10 µM). The heart rate in response to paxilline is the average of the peak responses following treatment. Toxins dissolved in Krebs-Henseleit solution were perfused through the heart for 12 min. Significance was tested using least significant difference post hoc test after analysis of variance. (C) Heart rate of isolated, perfused rat hearts infused with 0.23 µM iberiotoxin (IbTX) following a control infusion of Krebs-Henseleit fluid (n = 5). (D) Heart rate before treatment (saline control), at peak effect following infusion of iberiotoxin (n = 5), and following recovewry. Significance was tested using a paired Student's t-test. All data are mean ± S.E.M. *** P
    Figure Legend Snippet: The effect of paxilline and iberiotoxin on heart rate in the isolated rat heart. (A) 1 µM paxilline (Pax) was added at time = 40 min and infused for 10 min, preceded by a control infusion of Krebs-Henseleit perfusion fluid with 0.1% DMSO ( n = 5). (B) Heart rate before, during and after infusion at time zero of different concentrations of paxilline (1, 5 or 10 µM). The heart rate in response to paxilline is the average of the peak responses following treatment. Toxins dissolved in Krebs-Henseleit solution were perfused through the heart for 12 min. Significance was tested using least significant difference post hoc test after analysis of variance. (C) Heart rate of isolated, perfused rat hearts infused with 0.23 µM iberiotoxin (IbTX) following a control infusion of Krebs-Henseleit fluid (n = 5). (D) Heart rate before treatment (saline control), at peak effect following infusion of iberiotoxin (n = 5), and following recovewry. Significance was tested using a paired Student's t-test. All data are mean ± S.E.M. *** P

    Techniques Used: Isolation

    Cardiovascular function in wild-type (C57 black), Kcnmb1 −/ − , Kcnmb1/b4 −/− , and Kcnma1 −/− mice treated with 8 mg/kg paxilline (Pax). (A) Blood pressure and (B) Heart rate. ***, P
    Figure Legend Snippet: Cardiovascular function in wild-type (C57 black), Kcnmb1 −/ − , Kcnmb1/b4 −/− , and Kcnma1 −/− mice treated with 8 mg/kg paxilline (Pax). (A) Blood pressure and (B) Heart rate. ***, P

    Techniques Used: Mouse Assay

    11) Product Images from "GPR55 agonist lysophosphatidylinositol and lysophosphatidylcholine inhibit endothelial cell hyperpolarization via GPR-independent suppression of Na+-Ca2+ exchanger and endoplasmic reticulum Ca2+ refilling"

    Article Title: GPR55 agonist lysophosphatidylinositol and lysophosphatidylcholine inhibit endothelial cell hyperpolarization via GPR-independent suppression of Na+-Ca2+ exchanger and endoplasmic reticulum Ca2+ refilling

    Journal: Vascular pharmacology

    doi: 10.1016/j.vph.2017.01.002

    LPC16:0 produces hyperpolarization of EA.hy926 cells and activation of BK Ca channels independently G-protein coupled receptors. (A) Membrane potential recording showing the effect of 3 μM LPC16:0 on the membrane potential of EA.hy926 cells. (B) Representative whole-cell K + currents in response to voltage ramps from −80 to +80 mV in the absence (control), and presence of 3 μM LPC16:0 and in the combined presence of 3 μM LPC16:0 and 1 μM paxilline. Exemplary record out of 5 individual experiments.
    Figure Legend Snippet: LPC16:0 produces hyperpolarization of EA.hy926 cells and activation of BK Ca channels independently G-protein coupled receptors. (A) Membrane potential recording showing the effect of 3 μM LPC16:0 on the membrane potential of EA.hy926 cells. (B) Representative whole-cell K + currents in response to voltage ramps from −80 to +80 mV in the absence (control), and presence of 3 μM LPC16:0 and in the combined presence of 3 μM LPC16:0 and 1 μM paxilline. Exemplary record out of 5 individual experiments.

    Techniques Used: Activation Assay

    Related Articles

    other:

    Article Title: Blockade of BK channels attenuates chronic visceral hypersensitivity in an IBS-like rat model
    Article Snippet: Paxilline was purchased from Alomone Lab (Israel), the other drugs were purchased from Sigma Aldrich (USA).

    Article Title: Actions of FTY720 (Fingolimod), a Sphingosine-1-Phosphate Receptor Modulator, on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-Lymphocytes
    Article Snippet: Drugs and Solutions FTY720 (Fingolimod, Gilenya® , 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol hydrochloride, C19 H33 NO2 ), phytohemagglutinin (PHA), sphingosine-1-phosphate (S1P), tetrodotoxin and trypan blue were obtained from Sigma-Aldrich (St. Louis, MO, USA), nonactin, 9-phenanthrol, SEW2871 (5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-3-[3-(trifluoromethyl)phenyl]1,2,4-oxadiazole) and TRAM-34 (1-((2-chlorophenyl)(diphenyl))methyl)-1H -pyrazole) were from Tocris Cookson Ltd. (Bristol, UK), and paxilline was from Alomone Labs (Jerusalem, Israel).

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    Alomone Labs paxilline
    The RMP and EPSP of spinal cord lamina II neurons in IBS rats before and after the application of <t>paxilline.</t> (a) Representative action potential trace of an inhibitory interneuron. (b) Bar graph of the membrane potential of inhibitory neurons. Neurons, n = 11; animals, n = 9; ****: P
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    The RMP and EPSP of spinal cord lamina II neurons in IBS rats before and after the application of paxilline. (a) Representative action potential trace of an inhibitory interneuron. (b) Bar graph of the membrane potential of inhibitory neurons. Neurons, n = 11; animals, n = 9; ****: P

    Journal: Molecular Pain

    Article Title: Blockade of BK channels attenuates chronic visceral hypersensitivity in an IBS-like rat model

    doi: 10.1177/17448069211040364

    Figure Lengend Snippet: The RMP and EPSP of spinal cord lamina II neurons in IBS rats before and after the application of paxilline. (a) Representative action potential trace of an inhibitory interneuron. (b) Bar graph of the membrane potential of inhibitory neurons. Neurons, n = 11; animals, n = 9; ****: P

    Article Snippet: Paxilline was purchased from Alomone Lab (Israel), the other drugs were purchased from Sigma Aldrich (USA).

    Techniques:

    The sIPSCs and E/I of spinal cord lamina II neurons in IBS rats before and after application of paxilline. (a, b) Representative traces of sIPSC recorded from lamina II neurons in thoracolumbar spinal cord slices taken from IBS rats. (c, d) Bar graphs of the amplitude and frequency of sIPSCs in IBS rats. Neurons, n = 11; animals, n = 5 per group. (e) Representative traces of eEPSC (voltage clamped at −60 mv) and eIPSC (voltage clamped at 0 mv) recorded in the neuron of thoracolumbar spinal cord slice from IBS rats. The amplitude of eIPSCs increased after application of paxilline compared to the baseline. (f) Bar graph of the E/I ratio. Neurons, n = 8; animals, n = 5 per group; P = 0.0044. *: P

    Journal: Molecular Pain

    Article Title: Blockade of BK channels attenuates chronic visceral hypersensitivity in an IBS-like rat model

    doi: 10.1177/17448069211040364

    Figure Lengend Snippet: The sIPSCs and E/I of spinal cord lamina II neurons in IBS rats before and after application of paxilline. (a, b) Representative traces of sIPSC recorded from lamina II neurons in thoracolumbar spinal cord slices taken from IBS rats. (c, d) Bar graphs of the amplitude and frequency of sIPSCs in IBS rats. Neurons, n = 11; animals, n = 5 per group. (e) Representative traces of eEPSC (voltage clamped at −60 mv) and eIPSC (voltage clamped at 0 mv) recorded in the neuron of thoracolumbar spinal cord slice from IBS rats. The amplitude of eIPSCs increased after application of paxilline compared to the baseline. (f) Bar graph of the E/I ratio. Neurons, n = 8; animals, n = 5 per group; P = 0.0044. *: P

    Article Snippet: Paxilline was purchased from Alomone Lab (Israel), the other drugs were purchased from Sigma Aldrich (USA).

    Techniques:

    Effect of paxilline on rats. (a, b) Bar graphs of the EMG amplitude 30 min after spinal intrathecal injection of DMSO or paxilline (0.02, 0.2, 2, or 10 µM) with CRD at 40 mmHg or 60 mmHg in control rats, respectively; n = 6 per group. (c, d) Time curves of the effects of DMSO or paxilline (2 µM) at 40 and 60 mmHg CRD in control rats, respectively; n = 6 per group; *: P

    Journal: Molecular Pain

    Article Title: Blockade of BK channels attenuates chronic visceral hypersensitivity in an IBS-like rat model

    doi: 10.1177/17448069211040364

    Figure Lengend Snippet: Effect of paxilline on rats. (a, b) Bar graphs of the EMG amplitude 30 min after spinal intrathecal injection of DMSO or paxilline (0.02, 0.2, 2, or 10 µM) with CRD at 40 mmHg or 60 mmHg in control rats, respectively; n = 6 per group. (c, d) Time curves of the effects of DMSO or paxilline (2 µM) at 40 and 60 mmHg CRD in control rats, respectively; n = 6 per group; *: P

    Article Snippet: Paxilline was purchased from Alomone Lab (Israel), the other drugs were purchased from Sigma Aldrich (USA).

    Techniques: Injection

    Concentration-dependent effect of VP on I K(Ca) and the effects of different related compounds on VP-stimulated I K(Ca) in GH 3 cells. The experiments were conducted in cells bathed in normal Tyrode's solution and the depolarizing pulse from 0 to +50 mV [indicated in the upper part of (A) ] was delivered to the cell examined. (A) Superimposed I K(Ca) taken during step depolarization. a: control; b:1 μM VP; c: 3 μM VP; d: 10 μM VP. Arrowhead is the zero-current level and calibration bar refers to all traces. (B) Concentration-dependent effect of VP on I K(Ca) amplitude [mean ± SEM; n = 10–14 for each point (□)]. The examined cell was depolarized from 0 to +50 mV and current amplitude at the end of each depolarizing step was measured. As cells were exposed to 100 μM VP, I K(Ca) amplitude was taken to be 100%, and those at different VP concentrations were then compared. The values for EC 50 and the Hill coefficient were 2.4 μM and 1.1, respectively. Non-linear smooth line was least-squares fitted to a modified Hill function described in Materials and Methods . (C) Summary bar graph showing the effect of VP, VP plus tolbutamide, VP plus TRAM-39, VP plus paxilline, VP plus iberiotoxin, and VP plus dithiothreitol. Each bar showing I K(Ca) amplitude at the level of +60 mV indicates the mean ± SEM ( n = 11–14). *Significantly different from control ( P

    Journal: Frontiers in Chemistry

    Article Title: Characterization of Perturbing Actions by Verteporfin, a Benzoporphyrin Photosensitizer, on Membrane Ionic Currents

    doi: 10.3389/fchem.2019.00566

    Figure Lengend Snippet: Concentration-dependent effect of VP on I K(Ca) and the effects of different related compounds on VP-stimulated I K(Ca) in GH 3 cells. The experiments were conducted in cells bathed in normal Tyrode's solution and the depolarizing pulse from 0 to +50 mV [indicated in the upper part of (A) ] was delivered to the cell examined. (A) Superimposed I K(Ca) taken during step depolarization. a: control; b:1 μM VP; c: 3 μM VP; d: 10 μM VP. Arrowhead is the zero-current level and calibration bar refers to all traces. (B) Concentration-dependent effect of VP on I K(Ca) amplitude [mean ± SEM; n = 10–14 for each point (□)]. The examined cell was depolarized from 0 to +50 mV and current amplitude at the end of each depolarizing step was measured. As cells were exposed to 100 μM VP, I K(Ca) amplitude was taken to be 100%, and those at different VP concentrations were then compared. The values for EC 50 and the Hill coefficient were 2.4 μM and 1.1, respectively. Non-linear smooth line was least-squares fitted to a modified Hill function described in Materials and Methods . (C) Summary bar graph showing the effect of VP, VP plus tolbutamide, VP plus TRAM-39, VP plus paxilline, VP plus iberiotoxin, and VP plus dithiothreitol. Each bar showing I K(Ca) amplitude at the level of +60 mV indicates the mean ± SEM ( n = 11–14). *Significantly different from control ( P

    Article Snippet: Drugs and Solutions Verteporfin (VP, Visudyne®, BPD-MA, CL-318,952, C41 H42 N4 O8 ,), rose bengal, tetraethylammonium chloride (TEA), tetrodotoxin (TTX), and tolbutamide were acquired from Sigma-Aldrich (St. Louis, MO), iberiotoxin and paxilline from Alomone (Jerusalem, Israel), and A-803467 (5-(4-chlorophenyl)-N -(3,5-dimethoxyphenyl)-2-furancarboxamide), A-887826 (5-(4-butoxy-3-chlorophenyl)-N -[[2-(4-morpholinyl)-3-pyridinyl]methyl-3-pyridine carboxamide), 2-guanidine-4-methylquinazoline (GMQ), S(-)-Bay K 8644 (Bay K 8644), nifedipine, NS1619, PF573228 (3,4-dihydro-6-[[4-[[[3-(methylsulfonyl)phenyl]methyl]amino]-5-(trifluoromethyl)-2-pyrimidinyl]amino]-2(1H)-quinolinone) and TRAM-39 (2-cholo-α,α-diphenylbenzeneacetonitrile) were from Tocris Cookson Ltd. (Bristol, UK), and pioglitazone was obtained from Takeda (Tokyo, Japan).

    Techniques: Concentration Assay, Modification

    Stimulatory effect of QO-40 on the large-conductance Ca 2+ -activated K + (BK Ca ) channels identified in GH 3 cells. The single-channel experiments in an excised inside-out membrane patch were undertaken with symmetrical K + concentration (145 mM). The bath medium contained 0.1 μM Ca 2+ , and we kept the patch in voltage clamp at the level of +60 mV. ( A ) Representative current trace (upper, blue color) and the open probability (lower, red color) showing changes in the activity of BK Ca channels after addition of QO-40 (3 μM). Channel openings are indicated as upward deflections, and the horizontal bar shown above either current tracings or time course of single open probability corresponds to the application of QO-40 to the bath. The lower parts in ( A ) depict expanded records obtained from the dashed boxes in the uppermost part. Current traces in the left or right side indicate the absence or presence of 3 μM QO-40, respectively. Note that the presence of QO-40 leads to an increase in channel open-state probability of BK Ca channels. ( B ) BK Ca -channel activity obtained in the control period (i.e., neither QO-40 nor paxilline was present) (upper) and QO-40 (3 μM) plus paxilline (1 μM) (lower). In the experiments on QO-40 plus paxilline, paxilline (1 μM) was further added, as patch was continually exposed to QO-40 (3 μM). ( C ) Vertical scatter graph showing effects of QO-40, QO-40 plus TRAM-34, QO-40 plus linopirdine, or QO-40 plus paxilline on channel open-state probability of BK Ca channels (mean ± SEM; n = 8 for each point). Lino: 10 μM linopirdine; TRAM-34: 3 μM TRAM-34; Pax: 1 μM paxilline. Data analysis was performed by ANOVA-1 ( p

    Journal: Pharmaceuticals

    Article Title: Effective Activation of BKCa Channels by QO-40 (5-(Chloromethyl)-3-(Naphthalen-1-yl)-2-(Trifluoromethyl)Pyrazolo [1,5-a]pyrimidin-7(4H)-one), Known to Be an Opener of KCNQ2/Q3 Channels

    doi: 10.3390/ph14050388

    Figure Lengend Snippet: Stimulatory effect of QO-40 on the large-conductance Ca 2+ -activated K + (BK Ca ) channels identified in GH 3 cells. The single-channel experiments in an excised inside-out membrane patch were undertaken with symmetrical K + concentration (145 mM). The bath medium contained 0.1 μM Ca 2+ , and we kept the patch in voltage clamp at the level of +60 mV. ( A ) Representative current trace (upper, blue color) and the open probability (lower, red color) showing changes in the activity of BK Ca channels after addition of QO-40 (3 μM). Channel openings are indicated as upward deflections, and the horizontal bar shown above either current tracings or time course of single open probability corresponds to the application of QO-40 to the bath. The lower parts in ( A ) depict expanded records obtained from the dashed boxes in the uppermost part. Current traces in the left or right side indicate the absence or presence of 3 μM QO-40, respectively. Note that the presence of QO-40 leads to an increase in channel open-state probability of BK Ca channels. ( B ) BK Ca -channel activity obtained in the control period (i.e., neither QO-40 nor paxilline was present) (upper) and QO-40 (3 μM) plus paxilline (1 μM) (lower). In the experiments on QO-40 plus paxilline, paxilline (1 μM) was further added, as patch was continually exposed to QO-40 (3 μM). ( C ) Vertical scatter graph showing effects of QO-40, QO-40 plus TRAM-34, QO-40 plus linopirdine, or QO-40 plus paxilline on channel open-state probability of BK Ca channels (mean ± SEM; n = 8 for each point). Lino: 10 μM linopirdine; TRAM-34: 3 μM TRAM-34; Pax: 1 μM paxilline. Data analysis was performed by ANOVA-1 ( p

    Article Snippet: Chemicals and Solutions Used in This Work QO-40 (5-(chloromethyl)-3-(naphthalen-1-yl)-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-7(4H )-one, 5-(chloromethyl)-3-naphthalen-1-yl-2-(trifluoromethyl)-1H-pyrazolo[1,5-a]pyrimidin-7-one, C18 H11 ClF3 N3 O, https://www.alomone.com/p/qo-40/Q-265 , https://pubchem.ncbi.nlm.nih.gov/#query=QO-40 , accessed on 16 May 2011), and paxilline were acquired from Alomone (Asia Bioscience, Taipei, Taiwan).

    Techniques: Concentration Assay, Activity Assay

    Effects of linopirdine, TRAM-34, GAL-021, and paxilline on QO-40-stimulated I K(Ca) in GH 3 cells. In this set of experiments, whole-cell current recordings were undertaken in cells bathed in normal Tyrode’s solution, and the pipet was backfilled with K + -containing internal solution. ( A ) Representative I K(Ca) traces in the absence (a, blue color) and presence of either QO-40 (b, red color), QO-40 plus linopirdine (c, upper panel, green color), or QO-40 plus paxilline (c, lower panel, brown color). The uppermost part shows the voltage-clamp protocol used. ( B ) Vertical scatter graph showing effects of linopirdine, TRAM-34, GAL-021, or paxilline on QO-40-induced stimulation of I K(Ca) (mean ± SEM; n = 6–8 for each point). QO-40: 3 μM QO-40; Lino: 10 μM linopirdine; TRAM-34: 3 μM TRAM-34; GAL-021: 3 μM GAL-021; Pax: 1 μM paxilline. Data analysis was performed by ANOVA-1 ( p

    Journal: Pharmaceuticals

    Article Title: Effective Activation of BKCa Channels by QO-40 (5-(Chloromethyl)-3-(Naphthalen-1-yl)-2-(Trifluoromethyl)Pyrazolo [1,5-a]pyrimidin-7(4H)-one), Known to Be an Opener of KCNQ2/Q3 Channels

    doi: 10.3390/ph14050388

    Figure Lengend Snippet: Effects of linopirdine, TRAM-34, GAL-021, and paxilline on QO-40-stimulated I K(Ca) in GH 3 cells. In this set of experiments, whole-cell current recordings were undertaken in cells bathed in normal Tyrode’s solution, and the pipet was backfilled with K + -containing internal solution. ( A ) Representative I K(Ca) traces in the absence (a, blue color) and presence of either QO-40 (b, red color), QO-40 plus linopirdine (c, upper panel, green color), or QO-40 plus paxilline (c, lower panel, brown color). The uppermost part shows the voltage-clamp protocol used. ( B ) Vertical scatter graph showing effects of linopirdine, TRAM-34, GAL-021, or paxilline on QO-40-induced stimulation of I K(Ca) (mean ± SEM; n = 6–8 for each point). QO-40: 3 μM QO-40; Lino: 10 μM linopirdine; TRAM-34: 3 μM TRAM-34; GAL-021: 3 μM GAL-021; Pax: 1 μM paxilline. Data analysis was performed by ANOVA-1 ( p

    Article Snippet: Chemicals and Solutions Used in This Work QO-40 (5-(chloromethyl)-3-(naphthalen-1-yl)-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-7(4H )-one, 5-(chloromethyl)-3-naphthalen-1-yl-2-(trifluoromethyl)-1H-pyrazolo[1,5-a]pyrimidin-7-one, C18 H11 ClF3 N3 O, https://www.alomone.com/p/qo-40/Q-265 , https://pubchem.ncbi.nlm.nih.gov/#query=QO-40 , accessed on 16 May 2011), and paxilline were acquired from Alomone (Asia Bioscience, Taipei, Taiwan).

    Techniques:

    Single channel activity of high conductance elicited by NAGly in patches excised from mice aortic endothelium. (A) Exemplary traces showing single channel activity recording from a patch excised from the endothelium of mouse aorta before (Control) and after exposure to 3 μM NAGly. Outside-out configuration. Bath and pipette solution contained 3 μM free Ca 2+ and 140 mM KCl. Vm = +40 mV. (B) Current traces elicited by voltage ramps from − 100 to 100 mV in outside-out patch excised from mouse aortic endothelium and exposed to 3 μM NAGly. (C) Single channel activity from a patch excided from the endothelium of a NAGly-pre-treated strip at physiological voltages (− 40 mV and − 60 mV) and in the presence of 3 μM free Ca 2+ . Channel openings are shown as downward deflections. (D) Single channel activity from inside-out patch excised from the endothelium of NAGly (3 μM)-pretreated aortic strip before (control) and after exposure to paxilline (2 μM, n = 3). Vm = +60 mV, 3 μM free Ca 2+ .

    Journal: Vascular pharmacology

    Article Title: The quest for endothelial atypical cannabinoid receptor: BKCa channels act as cellular sensors for cannabinoids in in vitro and in situ endothelial cells

    doi: 10.1016/j.vph.2018.01.004

    Figure Lengend Snippet: Single channel activity of high conductance elicited by NAGly in patches excised from mice aortic endothelium. (A) Exemplary traces showing single channel activity recording from a patch excised from the endothelium of mouse aorta before (Control) and after exposure to 3 μM NAGly. Outside-out configuration. Bath and pipette solution contained 3 μM free Ca 2+ and 140 mM KCl. Vm = +40 mV. (B) Current traces elicited by voltage ramps from − 100 to 100 mV in outside-out patch excised from mouse aortic endothelium and exposed to 3 μM NAGly. (C) Single channel activity from a patch excided from the endothelium of a NAGly-pre-treated strip at physiological voltages (− 40 mV and − 60 mV) and in the presence of 3 μM free Ca 2+ . Channel openings are shown as downward deflections. (D) Single channel activity from inside-out patch excised from the endothelium of NAGly (3 μM)-pretreated aortic strip before (control) and after exposure to paxilline (2 μM, n = 3). Vm = +60 mV, 3 μM free Ca 2+ .

    Article Snippet: Paxilline and TRAM-34 were purchased from Alomone Labs.

    Techniques: Activity Assay, Mouse Assay, Transferring, Stripping Membranes

    NAGly and abn-cbd induce BK ca -dependent endothelial cell hyperpolarization in mouse aorta independently of gap junctions and GPR18. (A) A lack of effect of phenylephrine (1 μM) on the membrane potential of endothelial cells in isolated mouse aorta. Note that subsequent administration of Ach produces a hyperpolarization. (B) In the endothelium of isolated rat aorta, phenylephrine produces depolarization with membrane potential oscillations. (C) Effect of 10 μM NAGly (n = 5) on endothelial membrane potential in isolated mouse aorta. (D) Effect of 30 μM NAGly on endothelial membrane potential in isolated mouse aorta (n = 4). (E) Membrane potential recording showing the effect of paxilline (1 μM) on the hyperpolarization induced by NAGly (n = 3). (F) Membrane potential recording showing a failure of TRAM-34 to suppress the hyperpolarization to 10 μM abn-cbd in excised mouse aorta. (G) Intracellular perfusion with GPR18 antibody (1:500) fails to prevent endothelial cell hyperpolarization to 10 μM NAGly in isolated mouse aorta (n = 4). Recordings were commenced in the presence of 100 μM glycyrrhetinic acid, a gap junction inhibitor. (H) Bars showing the magnitude of shifts in endothelial membrane potential in isolated mice aorta induced by NAGly (10 μM and 30 μM) alone and combination of 10 μM NAGly and paxilline (1 μM) and GPR18 antibody. (I) Effect of NS1619 on the membrane potential of endothelial cells in excised mouse aorta. (J) Bars showing mean values of endothelial cell hyperpolarization to 10 μM (n = 6) and 30 μM NS1619 (n = 5).

    Journal: Vascular pharmacology

    Article Title: The quest for endothelial atypical cannabinoid receptor: BKCa channels act as cellular sensors for cannabinoids in in vitro and in situ endothelial cells

    doi: 10.1016/j.vph.2018.01.004

    Figure Lengend Snippet: NAGly and abn-cbd induce BK ca -dependent endothelial cell hyperpolarization in mouse aorta independently of gap junctions and GPR18. (A) A lack of effect of phenylephrine (1 μM) on the membrane potential of endothelial cells in isolated mouse aorta. Note that subsequent administration of Ach produces a hyperpolarization. (B) In the endothelium of isolated rat aorta, phenylephrine produces depolarization with membrane potential oscillations. (C) Effect of 10 μM NAGly (n = 5) on endothelial membrane potential in isolated mouse aorta. (D) Effect of 30 μM NAGly on endothelial membrane potential in isolated mouse aorta (n = 4). (E) Membrane potential recording showing the effect of paxilline (1 μM) on the hyperpolarization induced by NAGly (n = 3). (F) Membrane potential recording showing a failure of TRAM-34 to suppress the hyperpolarization to 10 μM abn-cbd in excised mouse aorta. (G) Intracellular perfusion with GPR18 antibody (1:500) fails to prevent endothelial cell hyperpolarization to 10 μM NAGly in isolated mouse aorta (n = 4). Recordings were commenced in the presence of 100 μM glycyrrhetinic acid, a gap junction inhibitor. (H) Bars showing the magnitude of shifts in endothelial membrane potential in isolated mice aorta induced by NAGly (10 μM and 30 μM) alone and combination of 10 μM NAGly and paxilline (1 μM) and GPR18 antibody. (I) Effect of NS1619 on the membrane potential of endothelial cells in excised mouse aorta. (J) Bars showing mean values of endothelial cell hyperpolarization to 10 μM (n = 6) and 30 μM NS1619 (n = 5).

    Article Snippet: Paxilline and TRAM-34 were purchased from Alomone Labs.

    Techniques: Isolation, Mouse Assay