Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres.

Abstract

Voltage clamp experiments studied the ionic basis of the strophanthidin-induced transient inward current (TI) which underlaid the transient depolarization associated with digitalis arrhythmia in calf cardiac Purkinje fibers. The reversal potential of TI (Erev) was determined in the presence of various bathing solutions. Erev averaged -5 mV in the standard modified Tyrode solution. Erev was displaced toward more negative potentials when the external Na concentration (Nao) was reduced by replacement of NaCl with Tris Cl, choline Cl or sucrose. A sudden reduction of Nao evoked a temporary increase in TI, followed after a few minutes by a sustained diminution. The initial increase was closely paralleled by an enhanced aftercontraction and could be explained by an indirect effect of Nao on internal Ca. The subsequent fall in TI amplitude may be accounted for by the reduced driving force, E-Erev. Erev was not significantly changed by replacing extracellular Cl with methylsulfate, or by limited variations in external Ca (2.7-16.2 mM) or external K (1-8 mM). These results are consistent with an increase in membrane permeability to Na and perhaps K. TI was not directly affected by TTX [tetrodotoxin], which blocks excitatory Na channels, or by Cs, which inhibits inwardly rectifying K channels. TI may be distinguished from the slow inward current by its kinetic, pharmacological and ionic properties. TI might be carried by a pre-existing ionic pathway such as the leak channel which provides inward current underlying normal pacemaker depolarization. Another possibility is that TI reflects Ca extrusion by an electrogenic Ca-Na exchange.