Transient inward current underlying arrhythmogenic effects of cardiotonic steroids in Purkinje fibres.

Abstract

Voltage-clamp experiments were carried out in calf Purkinje fibers to determine the basis of transient depolarizations (TDs) associated with digitalis-induced arrhythmias. Under the influence of strophanthidin, depolarizing clamp pulses were followed by a transient inward current (TI) which was small or absent in untreated preparations. The TI also appeared in the wake of a train of action potentials. It was designated TI because its magnitude and timing were appropriate to account for the TD. Longitudinal voltage non-uniformity during the TI was determined with 2 voltage-recording micro-electrodes. Although the non-uniformity was not severe, the TI wave form was observed when the voltage difference signal was used to measure membrane current density. Over the diastolic range of potential, the strophanthidin-induced TI appeared superimposed upon the normal pace-maker mechanism, the decay of a K current, iK2. The TI could be dissociated from iK2, however, by means of its unusual kinetic properties. TIs could also be recorded at holding potentials positive to -55 mV, i.e., outside the range where iK2 deactivation occurs. The TI amplitude showed a slow and strongly sigmoid dependence on the duration of the preceding depolarizing pulse. Stronger depolarizations increased the TI amplitude and speeded its development. Cooling reduced the TI amplitude, while slowing and exaggerating the sigmoid time-dependence. Two clamp pulses in close succession gave additive effects in evoking a subsequent TI. This finding and the sigmoid time-dependence fit with previous observations that TDs are most prominent following a series of closely spaced action potentials. The TI can help generate spontaneous depolarizations in preparations showing the low voltage oscillations which often occur with advanced digitalis toxicity.