Effects of propafenone on calcium currents in single ventricular myocytes of guinea-pig.
1. The effects of propafenone on the inward calcium current (ICa) were investigated in isolated single ventricular myocytes of the guinea-pig by the whole-cell clamp method. Propafenone inhibited ICa in a dose-dependent manner at concentrations of propafenone ranging from 1 x 10(-8) to 1 x 10(-3) M and half maximal block of ICa occurred at a propafenone concentration of 1.5 x 10(-6) M. Propafenone did not change the current-voltage relation of ICa other than a reduction in amplitude and showed no clear use- or frequency-dependent effects upon ICa (stimulation frequencies from 0.03 to 2 Hz). Propafenone did not alter the steady-state inactivation process: the half maximal activation potentials were 18.5 +/- 2.2 mV in the control state and 20.9 +/- 5.0 mV in the presence of 1 x 10(-6) M propafenone (n = 12, NS). Propafenone (1 x 10(-6) M) increased the half-time of reactivation by 73.9% (n = 6, 212.3 +/- 1.2 ms vs 369.2 +/- 1.5 ms, P < 0.05). 2. We conclude that propafenone blocks ICa in a concentration-dependent and a channel state-, use- or frequency-independent manner. The ICa blockade elicited by propafenone at clinically therapeutic plasma concentration is significant and may be involved in its anti-arrhythmic effects.
Department of Cardiological Sciences, St George's Hospital Medical School, London.
L
L
Fei
J S
JS
Gill
W J
WJ
McKenna
A J
AJ
Camm
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011405:Propafenone / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011405:Propafenone; D014700:Verapamil