Role of calcium ions in transient inward currents and aftercontractions induced by strophanthidin in cardiac Purkinje fibres.

Abstract

Under the influence of strophanthidin, Purkinje fibers [calf heart] exhibit transient inward current (TI) which contributes to arrhythmogenic activity. Voltage-clamp experiments were carried out to study the role of Ca ions in this phenomenon. The amplitude of TI varied directly with the extracellular Ca concentration, Cao. Mg ions had an antagonistic effect. TI was closely associated with a phasic increase in force (aftercontraction). Like TI, the aftercontraction was evoked by a preceding action potential or by the break of a strong depolarizing pulse. TI and the aftercontraction displayed similar wave forms although peak force current preceded peak force by 50-100 ms. Both transients were enhanced by increasing the strength or duration of the preceding depolarization pulse. Both events were slowed as the potential level following the pulse was displaced in the negative direction. TI and the aftercontraction may be evoked in the absence of cardiotonic steroids by strongly elevating Cao. The hypothesis that TI reflects an influx of Ca2+ ions was studied. Mn inhibited TI but the development and removal of the inhibition lagged far behind the effects on the slow inward current. TI may be suppressed and eventually inverted by varying the membrane potential in the positive direction. The inversion potential averaged -5 mV and was not consistent with a Ca-specific pathway. The aftercontraction was more closely related to the phasic conductance change underlying the current than to the current flow itself. An oscillatory release of Ca from an intracellular store apparently is the primary event underlying the aftercontraction and the conductance change which generates TI. Digitalis intoxication or very high Cao may promote such events by elevating intracellular Ca levels.