Slow inactivation of calcium channels in the cardiac Purkinje fiber

Voltage-dependent calcium channels exist in a wide variety of cells and participate in diverse aspects of cellular function [6]. In the heart, ion movement through these channels underlies impulse conduction in the atrioventricular and sinoatrial nodes, contributes to regulation of some ionic conductances, maintains the plateau phase of the ventricular and Purkinje fiber action potentials, and is linked to activation of contractile protein [4, 7, 11, 13]. The activation of this channel has been assumed to resemble activation of sodium channels but recent investigations have raised questions about the nature of its inactivation. In cardiac Purkinje fibers, Marban and Tsien [10] find that inactivation of this conductance is regulated, at least in part, by intracellular calcium, as is calcium channel inactivation in Helix and Aplysia neurones [14, 15] and Paramecium [2].In this paper, we report experiments designed to investigate another characteristic of calcium channel inactivation in the cardiac Purkinje fiber. Using a new procedure to reduce overlapping outward currents, we find a very slow component of inactivation in this channel. Time constants for this slow inactivation are on the order of seconds, are not steeply voltage dependent and are not regulated by calcium ion entry.