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Class III anti-arrhythmia drug E-4031 potentiates Na+/Ca2+ exchange current in rat ventricular myocytes
1Department of Physiology, Shanxi Medical University, Tai-yuan 030001, China.
Aim:
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.
Conclusion:
E-4031 stimulates the Na+/Ca2+ exchange via a protein kinase C-dependent pathway.