cyclic nucleotide gated channel hcn blocker zd 7288  (Tocris)

 
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    Structured Review

    Tocris cyclic nucleotide gated channel hcn blocker zd 7288
    AP threshold hyperpolarization persists with pharmacological blockade of I K , I A , I Ca and I h . A , left panel, Example traces recorded at baseline and after 25 min of APs evoked by a current ramp protocol (25 pA over 1 s) in a SC. Right panel, Summary AP threshold data for control conditions (black open circles; n = 6 cells) and in the presence of 2 mM TEA in the aCSF (red open circles; n = 5 cells). B , Superimposed first APs evoked by ramp protocol in control (black) and external TEA (red) conditions. TEA scaled to control (patch #181008p8). C , D , Same as A , B , but in the presence of 2 mM 4-AP (green lines; n = 5 cells; patch #181015p7). E , F , Same as A , B , but in the presence of 20 µM <t>ZD</t> <t>7288</t> (blue lines; n = 6 cells; patch #181018p2). G , H , Same as in A , B , but in the presence of 200–300 µM CdCl 2 (purple lines; n = 5 cells; patch #181024p4).
    Cyclic Nucleotide Gated Channel Hcn Blocker Zd 7288, supplied by Tocris, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Images

    1) Product Images from "Cerebellar Stellate Cell Excitability Is Coordinated by Shifts in the Gating Behavior of Voltage-Gated Na + and A-Type K + Channels"

    Article Title: Cerebellar Stellate Cell Excitability Is Coordinated by Shifts in the Gating Behavior of Voltage-Gated Na + and A-Type K + Channels

    Journal: eNeuro

    doi: 10.1523/ENEURO.0126-19.2019

    AP threshold hyperpolarization persists with pharmacological blockade of I K , I A , I Ca and I h . A , left panel, Example traces recorded at baseline and after 25 min of APs evoked by a current ramp protocol (25 pA over 1 s) in a SC. Right panel, Summary AP threshold data for control conditions (black open circles; n = 6 cells) and in the presence of 2 mM TEA in the aCSF (red open circles; n = 5 cells). B , Superimposed first APs evoked by ramp protocol in control (black) and external TEA (red) conditions. TEA scaled to control (patch #181008p8). C , D , Same as A , B , but in the presence of 2 mM 4-AP (green lines; n = 5 cells; patch #181015p7). E , F , Same as A , B , but in the presence of 20 µM ZD 7288 (blue lines; n = 6 cells; patch #181018p2). G , H , Same as in A , B , but in the presence of 200–300 µM CdCl 2 (purple lines; n = 5 cells; patch #181024p4).
    Figure Legend Snippet: AP threshold hyperpolarization persists with pharmacological blockade of I K , I A , I Ca and I h . A , left panel, Example traces recorded at baseline and after 25 min of APs evoked by a current ramp protocol (25 pA over 1 s) in a SC. Right panel, Summary AP threshold data for control conditions (black open circles; n = 6 cells) and in the presence of 2 mM TEA in the aCSF (red open circles; n = 5 cells). B , Superimposed first APs evoked by ramp protocol in control (black) and external TEA (red) conditions. TEA scaled to control (patch #181008p8). C , D , Same as A , B , but in the presence of 2 mM 4-AP (green lines; n = 5 cells; patch #181015p7). E , F , Same as A , B , but in the presence of 20 µM ZD 7288 (blue lines; n = 6 cells; patch #181018p2). G , H , Same as in A , B , but in the presence of 200–300 µM CdCl 2 (purple lines; n = 5 cells; patch #181024p4).

    Techniques Used:


    Structured Review

    Tocris hcn channel blocker zd 7288
    BC-2, characterized by a wider axonal than dendritic arbour ( A ), generated outward currents sensitive to TEA ( B , C ) and inward HCN currents (I HCN ; D ) sensitive to <t>ZD</t> <t>7288</t> ( E ). BC-2 responded to glutamate with comparatively small, bi-phasic inward currents ( F ). Accordingly, under zero-current clamp, glutamate caused an initial transient and a secondary, slow depolarization ( G ). The group of BC-2′ ( H ) expressed comparatively smaller outward and prominent sodium currents (I Na +) ( I ). HCN-currents and glutamate responses were similar between the two cell types ( J,K ).
    Hcn Channel Blocker Zd 7288, supplied by Tocris, used in various techniques. Bioz Stars score: 97/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Average 97 stars, based on 1 article reviews
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    hcn channel blocker zd 7288 - by Bioz Stars, 2023-02
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    Images

    1) Product Images from "Electrophysiological fingerprints of OFF bipolar cells in rat retina"

    Article Title: Electrophysiological fingerprints of OFF bipolar cells in rat retina

    Journal: Scientific Reports

    doi: 10.1038/srep30259

    BC-2, characterized by a wider axonal than dendritic arbour ( A ), generated outward currents sensitive to TEA ( B , C ) and inward HCN currents (I HCN ; D ) sensitive to ZD 7288 ( E ). BC-2 responded to glutamate with comparatively small, bi-phasic inward currents ( F ). Accordingly, under zero-current clamp, glutamate caused an initial transient and a secondary, slow depolarization ( G ). The group of BC-2′ ( H ) expressed comparatively smaller outward and prominent sodium currents (I Na +) ( I ). HCN-currents and glutamate responses were similar between the two cell types ( J,K ).
    Figure Legend Snippet: BC-2, characterized by a wider axonal than dendritic arbour ( A ), generated outward currents sensitive to TEA ( B , C ) and inward HCN currents (I HCN ; D ) sensitive to ZD 7288 ( E ). BC-2 responded to glutamate with comparatively small, bi-phasic inward currents ( F ). Accordingly, under zero-current clamp, glutamate caused an initial transient and a secondary, slow depolarization ( G ). The group of BC-2′ ( H ) expressed comparatively smaller outward and prominent sodium currents (I Na +) ( I ). HCN-currents and glutamate responses were similar between the two cell types ( J,K ).

    Techniques Used: Generated

    The axonal arbour of BC-3a stratifies across the second sublayer of the IPL ( A ). Its identity was further confirmed by HCN4 immunohistochemistry of previously recorded cells ( B , arrows). Note that the higher magnification images are from a different cell. Upon depolarization, BC-3a expressed outward currents of similar amplitude as BC-2′, but smaller Na + currents ( C ), while hyperpolarizing voltage steps activated HCN currents ( D ), sensitive to ZD 7288 ( E ). Glutamate stimuli triggered fast transient inward currents without a discernible secondary, sustained component ( F ). Voltage-clamped to 0 mV, glutamate stimulation evoked inhibitory responses ( G ) except in axotomized cells (inset; bars: 4 pA, 5s), which caused prolonged hyperpolarization under zero-current clamp, after an initial fast depolarization ( H ).
    Figure Legend Snippet: The axonal arbour of BC-3a stratifies across the second sublayer of the IPL ( A ). Its identity was further confirmed by HCN4 immunohistochemistry of previously recorded cells ( B , arrows). Note that the higher magnification images are from a different cell. Upon depolarization, BC-3a expressed outward currents of similar amplitude as BC-2′, but smaller Na + currents ( C ), while hyperpolarizing voltage steps activated HCN currents ( D ), sensitive to ZD 7288 ( E ). Glutamate stimuli triggered fast transient inward currents without a discernible secondary, sustained component ( F ). Voltage-clamped to 0 mV, glutamate stimulation evoked inhibitory responses ( G ) except in axotomized cells (inset; bars: 4 pA, 5s), which caused prolonged hyperpolarization under zero-current clamp, after an initial fast depolarization ( H ).

    Techniques Used: Immunohistochemistry

    BC-4 is morphologically characterized by the spread of its axonal arbour across the sublayers 1 and 2 of the IPL ( A ). After recording, its identity was immunohistochemically confirmed by calsenilin (Csen) labelling ( B , arrow). Increasingly depolarizing voltage steps caused first inward and subsequently outward currents with a large amount of synaptic noise, but no evident Na + currents ( C ). Hyperpolarization triggered non-inactivating inward currents insensitive to both nifedipine and ZD 7288, suggesting the presence of I Kir currents ( D ). In response to glutamate, a fast initial response is followed by a slowly developing secondary component under voltage clamp ( E ). Together with inhibitory feedback ( F ), this generates a complex triphasic response under current clamp ( G ).
    Figure Legend Snippet: BC-4 is morphologically characterized by the spread of its axonal arbour across the sublayers 1 and 2 of the IPL ( A ). After recording, its identity was immunohistochemically confirmed by calsenilin (Csen) labelling ( B , arrow). Increasingly depolarizing voltage steps caused first inward and subsequently outward currents with a large amount of synaptic noise, but no evident Na + currents ( C ). Hyperpolarization triggered non-inactivating inward currents insensitive to both nifedipine and ZD 7288, suggesting the presence of I Kir currents ( D ). In response to glutamate, a fast initial response is followed by a slowly developing secondary component under voltage clamp ( E ). Together with inhibitory feedback ( F ), this generates a complex triphasic response under current clamp ( G ).

    Techniques Used:


    Structured Review

    Tocris hcn channel blocker zd 7288
    Hcn Channel Blocker Zd 7288, supplied by Tocris, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/hcn channel blocker zd 7288/product/Tocris
    Average 94 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    hcn channel blocker zd 7288 - by Bioz Stars, 2023-02
    94/100 stars

    Images


    Structured Review

    Tocris hcn channel blocker zd 7288
    Hcn Channel Blocker Zd 7288, supplied by Tocris, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/hcn channel blocker zd 7288/product/Tocris
    Average 94 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    hcn channel blocker zd 7288 - by Bioz Stars, 2023-02
    94/100 stars

    Images


    Structured Review

    Tocris hcn channel blockers zd7288
    Hcn Channel Blockers Zd7288, supplied by Tocris, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/hcn channel blockers zd7288/product/Tocris
    Average 94 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    hcn channel blockers zd7288 - by Bioz Stars, 2023-02
    94/100 stars

    Images


    Structured Review

    Tocris hcn channel blocker zd 7288
    The Epac agonist 8-CPT enhances synaptic transmission. A, 8-CPT (50 μm) induced a modest increase in EJP amplitude (filled circles; n = 12) that was not blocked by the HCN channel inhibitor <t>ZD</t> <t>7288</t> (30 μm; open circles; n = 8). In five of the latter experiments, the PKA inhibitor KT 5720 (1 μm) was also present. ZD 7288 alone had no effect on transmission (open triangles; n = 4). B, With continuous perfusion of 8-CPT, forskolin (30 μm) increased EJP amplitudes further, resulting from HCN activation (filled circles; n = 3), and ZD 7288 depressed this effect (open circles; n = 3). The dotted line marks baseline EJP amplitudes in this and all subsequent figures.
    Hcn Channel Blocker Zd 7288, supplied by Tocris, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/hcn channel blocker zd 7288/product/Tocris
    Average 94 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    hcn channel blocker zd 7288 - by Bioz Stars, 2023-02
    94/100 stars

    Images

    1) Product Images from "cAMP Acts on Exchange Protein Activated by cAMP/cAMP-Regulated Guanine Nucleotide Exchange Protein to Regulate Transmitter Release at the Crayfish Neuromuscular Junction"

    Article Title: cAMP Acts on Exchange Protein Activated by cAMP/cAMP-Regulated Guanine Nucleotide Exchange Protein to Regulate Transmitter Release at the Crayfish Neuromuscular Junction

    Journal: The Journal of Neuroscience

    doi: 10.1523/JNEUROSCI.3703-04.2005

    The Epac agonist 8-CPT enhances synaptic transmission. A, 8-CPT (50 μm) induced a modest increase in EJP amplitude (filled circles; n = 12) that was not blocked by the HCN channel inhibitor ZD 7288 (30 μm; open circles; n = 8). In five of the latter experiments, the PKA inhibitor KT 5720 (1 μm) was also present. ZD 7288 alone had no effect on transmission (open triangles; n = 4). B, With continuous perfusion of 8-CPT, forskolin (30 μm) increased EJP amplitudes further, resulting from HCN activation (filled circles; n = 3), and ZD 7288 depressed this effect (open circles; n = 3). The dotted line marks baseline EJP amplitudes in this and all subsequent figures.
    Figure Legend Snippet: The Epac agonist 8-CPT enhances synaptic transmission. A, 8-CPT (50 μm) induced a modest increase in EJP amplitude (filled circles; n = 12) that was not blocked by the HCN channel inhibitor ZD 7288 (30 μm; open circles; n = 8). In five of the latter experiments, the PKA inhibitor KT 5720 (1 μm) was also present. ZD 7288 alone had no effect on transmission (open triangles; n = 4). B, With continuous perfusion of 8-CPT, forskolin (30 μm) increased EJP amplitudes further, resulting from HCN activation (filled circles; n = 3), and ZD 7288 depressed this effect (open circles; n = 3). The dotted line marks baseline EJP amplitudes in this and all subsequent figures.

    Techniques Used: Transmission Assay, Activation Assay

    LTG activates presynaptic HCN channels, but 8-CPT does not. A, Membrane potential (RMPaxon) recorded from a preterminal axon branch is unaffected by 8-CPT (50 μm; n = 3). B, LTG (50 μm) reversibly depolarized nerve terminals (n = 8). Superfusing ZD 7288 (30 μm) produced a 4-5 mV hyperpolarization resulting from block of the resting HCN activation (Beaumont and Zucker, 2000). ZD 7288 also blocked subsequent actions of LTG. C, HCN channels activated by hyperpolarizing current (500 msec) displayed a slowly relaxing afterdepolarization enhanced by LTG and blocked by ZD 7288. Sample recordings (C1) are shown for 40 nA currents: ZD 7288 reduced the afterdepolarization from 14 to 2.5 mV in the absence of LTG and from 22 to 6.9 mV in its presence. Dashed lines show the initial membrane potential (-74 mV); responses during the pulse were truncated. Plots (C2) indicate afterdepolarization amplitudes versus current magnitude in different solutions (n = 8 for each solution; the four sets of data are significantly different at p < 0.05 by ANOVA).
    Figure Legend Snippet: LTG activates presynaptic HCN channels, but 8-CPT does not. A, Membrane potential (RMPaxon) recorded from a preterminal axon branch is unaffected by 8-CPT (50 μm; n = 3). B, LTG (50 μm) reversibly depolarized nerve terminals (n = 8). Superfusing ZD 7288 (30 μm) produced a 4-5 mV hyperpolarization resulting from block of the resting HCN activation (Beaumont and Zucker, 2000). ZD 7288 also blocked subsequent actions of LTG. C, HCN channels activated by hyperpolarizing current (500 msec) displayed a slowly relaxing afterdepolarization enhanced by LTG and blocked by ZD 7288. Sample recordings (C1) are shown for 40 nA currents: ZD 7288 reduced the afterdepolarization from 14 to 2.5 mV in the absence of LTG and from 22 to 6.9 mV in its presence. Dashed lines show the initial membrane potential (-74 mV); responses during the pulse were truncated. Plots (C2) indicate afterdepolarization amplitudes versus current magnitude in different solutions (n = 8 for each solution; the four sets of data are significantly different at p < 0.05 by ANOVA).

    Techniques Used: Produced, Blocking Assay, Activation Assay

    The HCN channel agonist LTG activates the HNC-dependent portion of cAMP-dependent enhancement of synaptic transmission and LTG plus 8-CPT mimic forskolin action. A, LTG (50 μm) increased EJP amplitude modestly (filled circles; n = 5); this effect was blocked by ZD 7288 (open circles; n = 3). B, After LTG, forskolin enhanced EJP amplitudes by additional activation of HCN channels and by recruiting Epac activation (filled circles; n = 8); ZD 7288 reduced these responses to a level resembling Epac responses (open circles; n = 5). C, Concurrent HCN channel activation with LTG and Epac with 8-CPT produces a large EJP enhancement (filled circles; n = 8); ZD 7288 resulted in a response enhancement similar to the effect of Epac activation alone (open circles; n = 5). D, Forskolin occludes the enhancement by LTG and 8-CPT (n = 4). E, Sequential activation of HCN channels with LTG and Epac with 8-CPT (filled circles; n = 3) induced a smaller enhancement; ZD 7288 (open circles; n = 3) had no effect on the subsequent Epac responses.
    Figure Legend Snippet: The HCN channel agonist LTG activates the HNC-dependent portion of cAMP-dependent enhancement of synaptic transmission and LTG plus 8-CPT mimic forskolin action. A, LTG (50 μm) increased EJP amplitude modestly (filled circles; n = 5); this effect was blocked by ZD 7288 (open circles; n = 3). B, After LTG, forskolin enhanced EJP amplitudes by additional activation of HCN channels and by recruiting Epac activation (filled circles; n = 8); ZD 7288 reduced these responses to a level resembling Epac responses (open circles; n = 5). C, Concurrent HCN channel activation with LTG and Epac with 8-CPT produces a large EJP enhancement (filled circles; n = 8); ZD 7288 resulted in a response enhancement similar to the effect of Epac activation alone (open circles; n = 5). D, Forskolin occludes the enhancement by LTG and 8-CPT (n = 4). E, Sequential activation of HCN channels with LTG and Epac with 8-CPT (filled circles; n = 3) induced a smaller enhancement; ZD 7288 (open circles; n = 3) had no effect on the subsequent Epac responses.

    Techniques Used: Transmission Assay, Activation Assay

    BFA antagonizes Epac enhancement of transmission. A, The small G-protein antagonist BFA (100 μm) has no effect on synaptic transmission (n = 3). B, The enhancement of transmission by 50 μm 8-CPT (filled circles; from Fig. 1 A) was blocked by BFA (open circles; n = 5). C, The enhancement of transmission by 30 μm forskolin (filled circles; n = 9) was reduced to approximately one-half in BFA (open circles; n = 4). D, The enhancement by 50 μm LTG (filled circles; from Fig. 1C) was not blocked by BFA (open circles; n = 3). E, Concurrent application of BFA and 30 μm ZD 7288 (ZD) (open circles; n = 4) blocked fully the forskolin-induced enhancement of EJP amplitude (filled circles; n = 5).
    Figure Legend Snippet: BFA antagonizes Epac enhancement of transmission. A, The small G-protein antagonist BFA (100 μm) has no effect on synaptic transmission (n = 3). B, The enhancement of transmission by 50 μm 8-CPT (filled circles; from Fig. 1 A) was blocked by BFA (open circles; n = 5). C, The enhancement of transmission by 30 μm forskolin (filled circles; n = 9) was reduced to approximately one-half in BFA (open circles; n = 4). D, The enhancement by 50 μm LTG (filled circles; from Fig. 1C) was not blocked by BFA (open circles; n = 3). E, Concurrent application of BFA and 30 μm ZD 7288 (ZD) (open circles; n = 4) blocked fully the forskolin-induced enhancement of EJP amplitude (filled circles; n = 5).

    Techniques Used: Transmission Assay

    The role of Epac in the maintenance of enhanced transmission by cAMP and in synaptic tagging. A, The delayed addition of BFA antagonized the maintenance of synaptic enhancement by forskolin (n = 3). B, The delayed addition of ZD 7288 does not affect the maintained enhancement of transmission by forskolin, which only subsides when forskolin is removed (n = 4) (Beaumont et al., 2002). C, When forskolin enhancement is confined to HCN activation by BFA, the maintenance of this enhancement, which normally lasts as long as forskolin is present (filled circles; n = 4), is now sensitive to the delayed addition of ZD 7288 (ZD) (open circles; n = 3). D, The maintenance of forskolin enhancement by 8-CPT (filled circles) (from Fig. 3 A) was blocked by BFA (open circles; n = 3). E, The enhancement of EJP amplitude by forskolin at tagged synapses after LTF induction (filled circles; n = 3) was unaffected by ZD 7288 (open triangles; n = 5) but was inhibited by BFA (open circles; n = 3). F, The enhancement of transmission by 1 μm serotonin (5-HT; filled circles; n = 8) was reduced to approximately one-half by the combined block of HCN channel activation with ZD 7288 and Epac-dependent enhancement by BFA (open circles; n = 6).
    Figure Legend Snippet: The role of Epac in the maintenance of enhanced transmission by cAMP and in synaptic tagging. A, The delayed addition of BFA antagonized the maintenance of synaptic enhancement by forskolin (n = 3). B, The delayed addition of ZD 7288 does not affect the maintained enhancement of transmission by forskolin, which only subsides when forskolin is removed (n = 4) (Beaumont et al., 2002). C, When forskolin enhancement is confined to HCN activation by BFA, the maintenance of this enhancement, which normally lasts as long as forskolin is present (filled circles; n = 4), is now sensitive to the delayed addition of ZD 7288 (ZD) (open circles; n = 3). D, The maintenance of forskolin enhancement by 8-CPT (filled circles) (from Fig. 3 A) was blocked by BFA (open circles; n = 3). E, The enhancement of EJP amplitude by forskolin at tagged synapses after LTF induction (filled circles; n = 3) was unaffected by ZD 7288 (open triangles; n = 5) but was inhibited by BFA (open circles; n = 3). F, The enhancement of transmission by 1 μm serotonin (5-HT; filled circles; n = 8) was reduced to approximately one-half by the combined block of HCN channel activation with ZD 7288 and Epac-dependent enhancement by BFA (open circles; n = 6).

    Techniques Used: Transmission Assay, Activation Assay, Blocking Assay

    Epac activation substitutes for cAMP production in maintaining enhanced transmission, and Epac is the cAMP target at tagged synapses. A, 8-CPT (50 μm) maintained the enhancement of transmission produced by 30 μm forskolin (open circles; n = 6). B, The 8-CPT maintenance of enhancement was not blocked by delayed addition of 30 μm ZD 7288 (open circles; n = 6). The filled circles in A and B show responses to forskolin alone (n = 6). C, LTF, measured as an enhancement in EJP amplitude at least 20 min after the end of the tetanus, is induced by presynaptic stimulation at 20 Hz for 10 min in the absence of any drugs (filled green triangles; n = 9). LTF induced in the presence of Epac activation by 8-CPT was similar (filled red circles; n = 3). LTF in the presence of 8-CPT remained dependent on HCN activation and was blocked by ZD 7288 (open blue circles; n = 3). D, After LTF induction, synapses respond to forskolin (FSK) even when HCN channels are blocked, a process we call temporal synaptic tagging. 8-CPT strongly enhanced tagged synapses (filled red circles; n = 4), and this enhancement was insensitive to ZD 7288 (open blue circles; n = 4), just like responses to forskolin (open green triangles; n = 5).
    Figure Legend Snippet: Epac activation substitutes for cAMP production in maintaining enhanced transmission, and Epac is the cAMP target at tagged synapses. A, 8-CPT (50 μm) maintained the enhancement of transmission produced by 30 μm forskolin (open circles; n = 6). B, The 8-CPT maintenance of enhancement was not blocked by delayed addition of 30 μm ZD 7288 (open circles; n = 6). The filled circles in A and B show responses to forskolin alone (n = 6). C, LTF, measured as an enhancement in EJP amplitude at least 20 min after the end of the tetanus, is induced by presynaptic stimulation at 20 Hz for 10 min in the absence of any drugs (filled green triangles; n = 9). LTF induced in the presence of Epac activation by 8-CPT was similar (filled red circles; n = 3). LTF in the presence of 8-CPT remained dependent on HCN activation and was blocked by ZD 7288 (open blue circles; n = 3). D, After LTF induction, synapses respond to forskolin (FSK) even when HCN channels are blocked, a process we call temporal synaptic tagging. 8-CPT strongly enhanced tagged synapses (filled red circles; n = 4), and this enhancement was insensitive to ZD 7288 (open blue circles; n = 4), just like responses to forskolin (open green triangles; n = 5).

    Techniques Used: Activation Assay, Transmission Assay, Produced

    Enhancement of synaptic transmission by cAMP. A, Schematic of pathways enhancing transmission to cAMP and actions of agonists and antagonists. B, Effects of agonists activating Epac and HCN separately and together: green, 8-CPT activating Epac; blue, LTG activating HCN channels; orange, 8-CPT and LTG applied together; red, forskolin (from Figs. 1 A, 3A, C, and ​and5E).5E). C, Effects of antagonists of Epac and HCN separately and together on forskolin enhancement: green, ZD 7288 (ZD) blocking HCN channels and leaving Epac; blue, BFA blocking Epac and leaving HCN channels; black, ZD 7288 and BFA applied together; red, forskolin alone (from Fig. 5C, E) (Beaumont and Zucker, 2000).
    Figure Legend Snippet: Enhancement of synaptic transmission by cAMP. A, Schematic of pathways enhancing transmission to cAMP and actions of agonists and antagonists. B, Effects of agonists activating Epac and HCN separately and together: green, 8-CPT activating Epac; blue, LTG activating HCN channels; orange, 8-CPT and LTG applied together; red, forskolin (from Figs. 1 A, 3A, C, and ​and5E).5E). C, Effects of antagonists of Epac and HCN separately and together on forskolin enhancement: green, ZD 7288 (ZD) blocking HCN channels and leaving Epac; blue, BFA blocking Epac and leaving HCN channels; black, ZD 7288 and BFA applied together; red, forskolin alone (from Fig. 5C, E) (Beaumont and Zucker, 2000).

    Techniques Used: Transmission Assay, Blocking Assay

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    Tocris cyclic nucleotide gated channel hcn blocker zd 7288
    AP threshold hyperpolarization persists with pharmacological blockade of I K , I A , I Ca and I h . A , left panel, Example traces recorded at baseline and after 25 min of APs evoked by a current ramp protocol (25 pA over 1 s) in a SC. Right panel, Summary AP threshold data for control conditions (black open circles; n = 6 cells) and in the presence of 2 mM TEA in the aCSF (red open circles; n = 5 cells). B , Superimposed first APs evoked by ramp protocol in control (black) and external TEA (red) conditions. TEA scaled to control (patch #181008p8). C , D , Same as A , B , but in the presence of 2 mM 4-AP (green lines; n = 5 cells; patch #181015p7). E , F , Same as A , B , but in the presence of 20 µM <t>ZD</t> <t>7288</t> (blue lines; n = 6 cells; patch #181018p2). G , H , Same as in A , B , but in the presence of 200–300 µM CdCl 2 (purple lines; n = 5 cells; patch #181024p4).
    Cyclic Nucleotide Gated Channel Hcn Blocker Zd 7288, supplied by Tocris, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/cyclic nucleotide gated channel hcn blocker zd 7288/product/Tocris
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    Tocris hcn channel blocker zd 7288
    BC-2, characterized by a wider axonal than dendritic arbour ( A ), generated outward currents sensitive to TEA ( B , C ) and inward HCN currents (I HCN ; D ) sensitive to <t>ZD</t> <t>7288</t> ( E ). BC-2 responded to glutamate with comparatively small, bi-phasic inward currents ( F ). Accordingly, under zero-current clamp, glutamate caused an initial transient and a secondary, slow depolarization ( G ). The group of BC-2′ ( H ) expressed comparatively smaller outward and prominent sodium currents (I Na +) ( I ). HCN-currents and glutamate responses were similar between the two cell types ( J,K ).
    Hcn Channel Blocker Zd 7288, supplied by Tocris, used in various techniques. Bioz Stars score: 97/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/hcn channel blocker zd 7288/product/Tocris
    Average 97 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    hcn channel blocker zd 7288 - by Bioz Stars, 2023-02
    97/100 stars
      Buy from Supplier

    94
    Tocris hcn channel blockers zd7288
    BC-2, characterized by a wider axonal than dendritic arbour ( A ), generated outward currents sensitive to TEA ( B , C ) and inward HCN currents (I HCN ; D ) sensitive to <t>ZD</t> <t>7288</t> ( E ). BC-2 responded to glutamate with comparatively small, bi-phasic inward currents ( F ). Accordingly, under zero-current clamp, glutamate caused an initial transient and a secondary, slow depolarization ( G ). The group of BC-2′ ( H ) expressed comparatively smaller outward and prominent sodium currents (I Na +) ( I ). HCN-currents and glutamate responses were similar between the two cell types ( J,K ).
    Hcn Channel Blockers Zd7288, supplied by Tocris, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/hcn channel blockers zd7288/product/Tocris
    Average 94 stars, based on 1 article reviews
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    AP threshold hyperpolarization persists with pharmacological blockade of I K , I A , I Ca and I h . A , left panel, Example traces recorded at baseline and after 25 min of APs evoked by a current ramp protocol (25 pA over 1 s) in a SC. Right panel, Summary AP threshold data for control conditions (black open circles; n = 6 cells) and in the presence of 2 mM TEA in the aCSF (red open circles; n = 5 cells). B , Superimposed first APs evoked by ramp protocol in control (black) and external TEA (red) conditions. TEA scaled to control (patch #181008p8). C , D , Same as A , B , but in the presence of 2 mM 4-AP (green lines; n = 5 cells; patch #181015p7). E , F , Same as A , B , but in the presence of 20 µM ZD 7288 (blue lines; n = 6 cells; patch #181018p2). G , H , Same as in A , B , but in the presence of 200–300 µM CdCl 2 (purple lines; n = 5 cells; patch #181024p4).

    Journal: eNeuro

    Article Title: Cerebellar Stellate Cell Excitability Is Coordinated by Shifts in the Gating Behavior of Voltage-Gated Na + and A-Type K + Channels

    doi: 10.1523/ENEURO.0126-19.2019

    Figure Lengend Snippet: AP threshold hyperpolarization persists with pharmacological blockade of I K , I A , I Ca and I h . A , left panel, Example traces recorded at baseline and after 25 min of APs evoked by a current ramp protocol (25 pA over 1 s) in a SC. Right panel, Summary AP threshold data for control conditions (black open circles; n = 6 cells) and in the presence of 2 mM TEA in the aCSF (red open circles; n = 5 cells). B , Superimposed first APs evoked by ramp protocol in control (black) and external TEA (red) conditions. TEA scaled to control (patch #181008p8). C , D , Same as A , B , but in the presence of 2 mM 4-AP (green lines; n = 5 cells; patch #181015p7). E , F , Same as A , B , but in the presence of 20 µM ZD 7288 (blue lines; n = 6 cells; patch #181018p2). G , H , Same as in A , B , but in the presence of 200–300 µM CdCl 2 (purple lines; n = 5 cells; patch #181024p4).

    Article Snippet: Additional current-clamp experiments were performed in the presence of hyperpolarization-activated cyclic nucleotide-gated channel (HCN) blocker ZD 7288 in the aCSF (20 µM; Tocris Bioscience).

    Techniques:

    BC-2, characterized by a wider axonal than dendritic arbour ( A ), generated outward currents sensitive to TEA ( B , C ) and inward HCN currents (I HCN ; D ) sensitive to ZD 7288 ( E ). BC-2 responded to glutamate with comparatively small, bi-phasic inward currents ( F ). Accordingly, under zero-current clamp, glutamate caused an initial transient and a secondary, slow depolarization ( G ). The group of BC-2′ ( H ) expressed comparatively smaller outward and prominent sodium currents (I Na +) ( I ). HCN-currents and glutamate responses were similar between the two cell types ( J,K ).

    Journal: Scientific Reports

    Article Title: Electrophysiological fingerprints of OFF bipolar cells in rat retina

    doi: 10.1038/srep30259

    Figure Lengend Snippet: BC-2, characterized by a wider axonal than dendritic arbour ( A ), generated outward currents sensitive to TEA ( B , C ) and inward HCN currents (I HCN ; D ) sensitive to ZD 7288 ( E ). BC-2 responded to glutamate with comparatively small, bi-phasic inward currents ( F ). Accordingly, under zero-current clamp, glutamate caused an initial transient and a secondary, slow depolarization ( G ). The group of BC-2′ ( H ) expressed comparatively smaller outward and prominent sodium currents (I Na +) ( I ). HCN-currents and glutamate responses were similar between the two cell types ( J,K ).

    Article Snippet: The L-type Ca 2+ channel blocker nifedipine (30 μM, Sigma-Aldrich), the K + channel blocker TEA (10 mM, Merck), the HCN channel blocker ZD 7288 (50 μM, Tocris), the NO donor NOC-12 (200 μM, Calbiochem) and the membrane-permeable cyclic GMP analogue 8-Br-cGMP (1 mM, Sigma-Aldrich) were applied to the IPL from single or triple barrel glass pipettes.

    Techniques: Generated

    The axonal arbour of BC-3a stratifies across the second sublayer of the IPL ( A ). Its identity was further confirmed by HCN4 immunohistochemistry of previously recorded cells ( B , arrows). Note that the higher magnification images are from a different cell. Upon depolarization, BC-3a expressed outward currents of similar amplitude as BC-2′, but smaller Na + currents ( C ), while hyperpolarizing voltage steps activated HCN currents ( D ), sensitive to ZD 7288 ( E ). Glutamate stimuli triggered fast transient inward currents without a discernible secondary, sustained component ( F ). Voltage-clamped to 0 mV, glutamate stimulation evoked inhibitory responses ( G ) except in axotomized cells (inset; bars: 4 pA, 5s), which caused prolonged hyperpolarization under zero-current clamp, after an initial fast depolarization ( H ).

    Journal: Scientific Reports

    Article Title: Electrophysiological fingerprints of OFF bipolar cells in rat retina

    doi: 10.1038/srep30259

    Figure Lengend Snippet: The axonal arbour of BC-3a stratifies across the second sublayer of the IPL ( A ). Its identity was further confirmed by HCN4 immunohistochemistry of previously recorded cells ( B , arrows). Note that the higher magnification images are from a different cell. Upon depolarization, BC-3a expressed outward currents of similar amplitude as BC-2′, but smaller Na + currents ( C ), while hyperpolarizing voltage steps activated HCN currents ( D ), sensitive to ZD 7288 ( E ). Glutamate stimuli triggered fast transient inward currents without a discernible secondary, sustained component ( F ). Voltage-clamped to 0 mV, glutamate stimulation evoked inhibitory responses ( G ) except in axotomized cells (inset; bars: 4 pA, 5s), which caused prolonged hyperpolarization under zero-current clamp, after an initial fast depolarization ( H ).

    Article Snippet: The L-type Ca 2+ channel blocker nifedipine (30 μM, Sigma-Aldrich), the K + channel blocker TEA (10 mM, Merck), the HCN channel blocker ZD 7288 (50 μM, Tocris), the NO donor NOC-12 (200 μM, Calbiochem) and the membrane-permeable cyclic GMP analogue 8-Br-cGMP (1 mM, Sigma-Aldrich) were applied to the IPL from single or triple barrel glass pipettes.

    Techniques: Immunohistochemistry

    BC-4 is morphologically characterized by the spread of its axonal arbour across the sublayers 1 and 2 of the IPL ( A ). After recording, its identity was immunohistochemically confirmed by calsenilin (Csen) labelling ( B , arrow). Increasingly depolarizing voltage steps caused first inward and subsequently outward currents with a large amount of synaptic noise, but no evident Na + currents ( C ). Hyperpolarization triggered non-inactivating inward currents insensitive to both nifedipine and ZD 7288, suggesting the presence of I Kir currents ( D ). In response to glutamate, a fast initial response is followed by a slowly developing secondary component under voltage clamp ( E ). Together with inhibitory feedback ( F ), this generates a complex triphasic response under current clamp ( G ).

    Journal: Scientific Reports

    Article Title: Electrophysiological fingerprints of OFF bipolar cells in rat retina

    doi: 10.1038/srep30259

    Figure Lengend Snippet: BC-4 is morphologically characterized by the spread of its axonal arbour across the sublayers 1 and 2 of the IPL ( A ). After recording, its identity was immunohistochemically confirmed by calsenilin (Csen) labelling ( B , arrow). Increasingly depolarizing voltage steps caused first inward and subsequently outward currents with a large amount of synaptic noise, but no evident Na + currents ( C ). Hyperpolarization triggered non-inactivating inward currents insensitive to both nifedipine and ZD 7288, suggesting the presence of I Kir currents ( D ). In response to glutamate, a fast initial response is followed by a slowly developing secondary component under voltage clamp ( E ). Together with inhibitory feedback ( F ), this generates a complex triphasic response under current clamp ( G ).

    Article Snippet: The L-type Ca 2+ channel blocker nifedipine (30 μM, Sigma-Aldrich), the K + channel blocker TEA (10 mM, Merck), the HCN channel blocker ZD 7288 (50 μM, Tocris), the NO donor NOC-12 (200 μM, Calbiochem) and the membrane-permeable cyclic GMP analogue 8-Br-cGMP (1 mM, Sigma-Aldrich) were applied to the IPL from single or triple barrel glass pipettes.

    Techniques: