Class III anti-arrhythmia drug E-4031 potentiates Na+/Ca2+ exchange current in rat ventricular myocytes.
OBJECTIVE
To study the effects of E-4031 on the Na+/Ca2+ exchange currents (INa/Ca).


METHODS
The quasi-steady state current-voltage relationship from the isolated rat ventricular myocytes was measured using whole-cell voltage-clamp techniques with a ramp pulse protocol.


RESULTS
At potential of  mV, E-4031 5, 10, and 20 mumol.L-1 increased Ni(2+)-sensitive current from (0.48 +/- 0.12), to (0.78 +/- 0.20), (0.96 +/- 0.16), and (1.15 +/- 0.13) pA/pF, respectively; tetradecanoylphorbol acetate (TPA) 50 nmol.L-1 increased Ni(2+)-sensitive current from (0.60 +/- 0.16) to (1.33 +/- 0.25) pA/pF. Tamoxifen 20 mumol.L-1 completely prevented the current changes induced by E-4031 and TPA.


CONCLUSIONS
E-4031 stimulates the Na+/Ca2+ exchange via a protein kinase C-dependent pathway.
Wu
D M
DM
Department of Physiology, Shanxi Medical University, Tai-yuan 030001, China.
Lu
J Y
JY
Wu
B W
BW
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002469:Cell Separation; D006352:Heart Ventricles; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D011725:Pyridines; D019831:Sodium-Calcium Exchanger; D013629:Tamoxifen; C063968:E 4031; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate