Caffeine induces a transient inward current in cultured cardiac cells

Abstract

Electrical excitation of cardiac muscle may sometimes be due to initiation of inward current by the presence of Ca²⁺ ions at the inner surface of the cell membrane. During digitalis toxicity and other conditions that abnormally augment cellular Ca²⁺ stores, premature release of Ca²⁺ from the sarcoplasmic retkulum leads to a transient inward current, which is large enough to initiate premature beats and is accompanied by a transient contractile response^1–5 This inward current may be mediated either by electrogenic sodium–calcium exchange⁶ or by specific Ca²⁺-activated cation channels that have recently been characterized in tissue cultures of cardiac myocytes⁷. An obvious question raised by these observations is whether release of the sequestered Ca²⁺ stores during each normal beat exerts a similar influence on membrane potential. To explore this, chick embryonic myocardial cell aggregates were voltage-clamped during abrupt exposure to caffeine, which is known to release Ca²⁺ from the sarcoplasmic reticulum^8–10. The speed of the perfusion system and the relative absence of diffusion barriers in the tissue-cultured cells allowed the effects of caffeine-induced Ca²⁺ release to be studied on a time scale comparable to that of a single normal beat. We report here that abrupt exposure of the cells to caffeine produced a transient inward current having similar features to that of digitalis toxicity, and which was both large enough and rapid enough to potentially contribute to the action potential.