Article date: May 1993
By: Lü Fei, Jaswinder S. Gill, William J. McKenna, A. John Camm, in Volume 109, Issue 1, pages 178-182
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 × 10−8 to 1 × 10−3m and half maximal block of ICa occurred at a propafenone concentration of 1.5 × 10−6m. 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 1×10−6m propafenone (n = 12, NS). Propafenone (1 × 10−6m) 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).
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.
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 × 10−8 to 1 × 10−3m and half maximal block of ICa occurred at a propafenone concentration of 1.5 × 10−6m. 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 1×10−6m propafenone (n = 12, NS). Propafenone (1 × 10−6m) 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).
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.
DOI: 10.1111/j.1476-5381.1993.tb13550.x
View this article