P-94 - Effects of goniopora toxin on the action potential and membrane currents of guinea-pig single ventricular cells

Abstract

The effects of Goniopora toxin (GPT), a polypeptide isolated from a coral, Goniopora spp., on action potential and membrane currents were studied in single ventricular cells of the guinea-pig using the whole-cell clamp technique with a single patch electrode. GPT at a concentration of 10 nmol/l prolonged the duration of the action potential without significant change in the resting membrane potential and action potential amplitudes. This prolongation became more evident at lower stimulus frequencies and persisted after washing with toxin-free solution. Tetrodotoxin (TTX, 1 μmol/l), but not Co2+ (2 mmol/1), abolished the prolonged action potential. Under voltage-clamp conditions, a sustained inward current, not present in the control, followed the transient inward current during depolarizing pulses in the GPT-treated cells. The current-voltage relationship for the sustained inward current was much the same as that for the fast sodium current reported in rat single ventricular cells (Brown et al. 1981). Both the sustained and transient currents were abolished by the shift of holding potential in the direction of depolarization and reappeared after repolarization; the reappearance of the sustained current was much slower than that of the transient current. TTX but not Co2+ abolished both the sustained and transient inward currents. Calcium current and time-independent current were not affected by GPT. Time-dependent outward current induced by large depolarizing pulses was attenuated by GPT. From these results, it is suggested that GPT predominantly acts on the sodium channels in cardiac muscle, to give rise to a sustained sodium current which is responsible for the prolongation of action potential, and that the sodium channels modified by this toxin may reveal slow inactivation and slow recovery from inactivation as compared with those of unmodified sodium channels.