Journal: BMC Pharmacology & Toxicology

Article Title: Electrophysiological analysis of mammalian cells expressing hERG using automated 384-well-patch-clamp

doi: 10.1186/s40360-015-0042-9

Figure Lengend Snippet: Inhibition of hERG currents by various hERG channel blockers. hERG currents on HEK 293 cells expressed hERG gene were detected by an automated 384-well-patch-clamp system. hERG currents were inhibited concentration-dependently by five hERG channel blockers, astemizole ( a ), cisapride ( b ), E-4031 ( c ), quinidine ( d ), and terfenadine ( e ). Left and right panels show the representative recordings of hERG current inhibition and the inhibitory curves of hERG currents, respectively. The 50 % inhibitory concentrations (IC 50 ) were analyzed and shown in the left upper sides of the right panels. The n numbers were total numbers of cells at all concentrations of each drug. Three hundred eighty-four points were divided into six, and five hERG channel blockers and no blocker were added. The error bars in the right panels show means ± SD and IC 50 values show means

Article Snippet: In this study, five hERG channel blockers [astemizole (Sigma-Aldrich, St. Louis, MO, USA), cisapride monohydrate (Sigma-Aldrich), E-4031 hydrochloride (Wako pure chemical, Tokyo, Japan), quinidine (Sigma-Aldrich), and terfenadine (Sigma-Aldrich)] were used.

Techniques: Inhibition, Patch Clamp, Concentration Assay

Journal: BMC Pharmacology & Toxicology

Article Title: Electrophysiological analysis of mammalian cells expressing hERG using automated 384-well-patch-clamp

doi: 10.1186/s40360-015-0042-9

Figure Lengend Snippet: IC50 of hERG channel blockers

Article Snippet: In this study, five hERG channel blockers [astemizole (Sigma-Aldrich, St. Louis, MO, USA), cisapride monohydrate (Sigma-Aldrich), E-4031 hydrochloride (Wako pure chemical, Tokyo, Japan), quinidine (Sigma-Aldrich), and terfenadine (Sigma-Aldrich)] were used.

Techniques:

Journal: bioRxiv

Article Title: hiPSC-CM Electrophysiology: Impact of Temporal Changes and Study Parameters on Experimental Reproducibility

doi: 10.1101/2023.10.02.560475

Figure Lengend Snippet: hiPSC-CM electrophysiology data was collected (4 vs 10 days post-defrost) at baseline and after exposure to a hERG channel blocker (E-4031), calcium channel blocker (nifedipine), or beta-adrenergic agonist (isoproterenol). A) Percent change in the spontaneous beating rate, normalized to baseline measurement (repeated-measures) after 15-minute drug treatment. B) Representative traces of spontaneous beating after drug treatment. C-E) Percent change in the field potential duration, spike amplitude, and conduction velocity (normalized to baseline measurement) after 15-minute drug treatment. hiPSC-CMs were externally paced to normalize the beating rate (1.5 Hz for E-4031 which slowed the intrinsic rate; 3 Hz for nifedipine and isoproterenol which increased the intrinsic rate). F-H) Percent change in the action potential duration at 30%, 50%, and 90% repolarization (normalized to baseline measurement) after 15-minute drug treatment. hiPSC-CMs were externally paced to normalize the beating rate (1.5 Hz for E-4031; 2 Hz for nifedipine and isoproterenol). Measurements are shown as a Tukey box-and-whisker plot. Unpaired Student’s t-test, two tailed. *p<0.05, **p<0.01, ****p<0.0001. Number of replicates indicated.

Article Snippet: A hERG channel blocker (50 nM E-4031, #15203 Cayman Chemical) was tested for its ability to prolong FPD and APD( , , ).

Techniques: Whisker Assay, Two Tailed Test

Journal: PLoS ONE

Article Title: Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block

doi: 10.1371/journal.pone.0163619

Figure Lengend Snippet: The ECG “signature” of selective hERG potassium channel block is shown as the relationship between predicted drug-induced placebo-corrected changes from baseline in QTc and (a) J-T peak c, (b) Tpeak-Tend, (c) 30% of early repolarization duration, (d) 30% of late repolarization duration, (e) T-wave flatness, (f) T-wave asymmetry and (g) T-wave amplitude. Average predictions (dots) and 95% confidence intervals (horizontal and vertical lines) are from the concentration-dependent models for QTc (x axis) and the different T-wave morphology biomarkers (y axis) at 25% increments of the population’s Cmax for dofetilide alone (light gray) and moxifloxacin (yellow) arms in this study together with the dofetilide arm from previous clinical study (Dofetilide—Study 1) [ , ]. QTc, Fridericia’s heart rate corrected QT; J-T peak c, heart rate corrected J-T peak c interval.

Article Snippet: In each treatment period subjects were dosed three times during the day with placebo, a selective hERG potassium channel blocker (dofetilide [Tikosyn, Pfizer, USA] or moxifloxacin) or a late sodium current blocker (mexiletine [Teva Pharmaceuticals USA Inc.,USA] or lidocaine [B. Braun Medical, Inc., USA]) alone or in combination (mexiletine combined with dofetilide, lidocaine combined with dofetilide), or a selective hERG potassium channel blocker (moxifloxacin) alone or in combination with a calcium channel blocker (diltiazem).

Techniques: Blocking Assay, Concentration Assay

Journal: PLoS ONE

Article Title: Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block

doi: 10.1371/journal.pone.0163619

Figure Lengend Snippet: The decision tree classifies the drug effects on any ECG from any time point based on the time-matched placebo-corrected changes from baseline (ΔΔ) as selective of predominant hERG potassium channel block (right bin), multichannel block (left bin) or inconclusive (middle bin). More specifically, if ΔΔJ-T peak c is greater than 9ms the ECG is classified as predominant or selective hERG potassium channel block. If ΔΔ J-T peak c is less than or equal to 9ms and ΔΔQTc less than or equal to 29ms, then the ECG is classified as multichannel block. Otherwise the classification is inconclusive. The number of ECGs from each class in the training set is reported in parenthesis on top of each class bin. The percentage of ECGs correctly classified within each class is reported below each class bin. See text for more details on classification performance in both training (hERG [dofetilide and moxifloxacin] vs. multichannel [dofetilide + mexiletine and dofetilide + lidocaine]) and validation (hERG [dofetilide and quinidine] vs. multichannel [ranolazine and verapamil]) sets. QTc, Fridericia’s heart rate corrected QT interval; J-T peak c, heart rate corrected J-T peak interval; hERG, selective or strong hERG potassium channel block; Multichannel, inward (late sodium or calcium) current and hERG potassium channel block.

Article Snippet: In each treatment period subjects were dosed three times during the day with placebo, a selective hERG potassium channel blocker (dofetilide [Tikosyn, Pfizer, USA] or moxifloxacin) or a late sodium current blocker (mexiletine [Teva Pharmaceuticals USA Inc.,USA] or lidocaine [B. Braun Medical, Inc., USA]) alone or in combination (mexiletine combined with dofetilide, lidocaine combined with dofetilide), or a selective hERG potassium channel blocker (moxifloxacin) alone or in combination with a calcium channel blocker (diltiazem).

Techniques: Blocking Assay