Different time courses of the blockade of sodium current by lignocaine and SUN 1165 in single myocytes isolated from guinea‐pig atrium

1 The time course of the blockade of sodium currents (INa) by the antiarrhythmic agents, lignocaine and SUN 1165, was studied in single myocytes isolated enzymatically from guinea‐pig atrium, by a new concentration‐jump termed as a ‘concentration‐clamp’ technique. This technique combines an intracellular perfusion and a rapid exchange of external solution surrounding the voltage‐clamped myocyte within 2 ms. 2 Lignocaine (3.7 × 10−5 m to 3.7 × 10−4 M) inhibited the peak amplitude of INa in a concentration‐dependent fashion. It took 2 to 5 s to reach apparent steady‐state inhibition at the concentrations used. Complete recovery from the inhibition also took 2 to 5 s after washing out the agent. In contrast, the inhibitory effect of SUN 1165 (1 × 10−5 M) on the peak INa gradually progressed and reached a steady‐state level about 2 min after the start of drug‐application. The recovery required more than 10 min after washing out of the agent. 3 In cardiomyocytes treated with scorpion toxin (5 μg ml−1), the inactivation of INa was greatly inhibited, resulting in the relatively persistent Na inward current (persistent INa) during the depolarizing pulse. Lignocaine (1.1 × 10−4 M) applied during the depolarizing pulse, reduced in a single‐exponential fashion the amplitude of the persistent INa in milliseconds. On the other hand, lignocaine applied several tens of milliseconds before the depolarizing pulse induced only a small reduction of the peak amplitude of the first persistent INa. When SUN 1165 (1 × 10−5 M) was applied during the depolarizing pulse, there was only a small instantaneous reduction of the amplitude of the persistent INa, although it did inhibit time‐dependently, the peak INa. Both agents accelerated the decay phase of the persistent INa in a time‐dependent manner. 4 These results suggest that lignocaine and SUN 1165 may preferentially interact with the open‐state of the sodium channel rather than with the rested one, although SUN 1165 does so much more slowly.