EFFECTS OF PROPAFENONE ON CALCIUM CURRENT IN GUINEA-PIG VENTRICULAR MYOCYTES

1 The modulation of L-type voltage-sensitive calcium channels in guinea-pig isolated ventricular myocytes by propafenone was examined by the whole cell voltage-clamp technique. 2 Propafenone, 10(-7)-5 x 10(-5) M, produced a concentration-dependent inhibition of Ca current (I(Ca)) without any significant change in the current-voltage relation. Half-blocking concentration (IC50) of propafenone for the peak I(Ca) at + 10 mV was 5 x 10(-6) M. 3 The voltage-dependence of I(Ca) inactivation was shifted in the hyperpolarizing direction in the presence of 5 x 10(-6) M propafenone. 4 A frequency-dependent relative block by propafenone was observed after repetitive depolarizing test pulses at a frequency of 0.5 and 1 Hz. The recovery of I(Ca) from inactivation was prolonged by propafenone and the reactivation exhibited an additional exponential component attributed to the slow release from drug block of Ca channels. 5 These results suggest that propafenone, at therapeutic concentrations exhibits Ca channel blocking properties that may be involved in its antiarrhythmic mechanism.