Effect of tetrodotoxin on action potentials of the conducting system in the dog heart

Abstract

Tetrodotoxin (TTX) shortens Purkinje fiber action potential duration (APD) at concentrations (greater than or equal to 3.3 x 10(-8) M) lower than that at which the maximum rate of rise decreases (approximately 10(-6) M). The shortening effect of TTX occurs either at low or high driving rate and is much greater in Purkinje fibers than in bundle branch and muscle fibers. As a result, at a TTX concentration of 1.3 x 10(-6) M, the APD is no longer statistically different all along the conducting system, i.e., the gating mechanism described by Myerburg et al. (Circ. Res. 26: 361-378, 1970) is suppressed. It is concluded that this gating mechanism is attributable, at least in part, to the existence of a TTX-sensitive inward sodium current lengthening the plateau of the Purkinje fiber action potential. Our experimental results and reconstruction of Purkinje fiber action potentials suggest that this current, which is more sensitive to TTX than the normal rapid sodium current, flows through a background sodium conductance or/and a small proportion of sodium channels with no inactivation mechanism (or inactivation mechanism different from normal). The importance of this finding for the mechanism of action of antiarrhythmic drugs is pointed out.