Caffeine induces a transient inward current in cultured cardiac cells

Electrical excitation of cardiac muscle may sometimes be due to initiation of inward current by the presence of Ca 2+ ions at the inner surface of the cell membrane. During digitalis toxicity and other conditions that abnormally augment cellular Ca 2+ stores, premature release of Ca 2+ 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 exchange 6 or by specific Ca 2+ -activated cation channels that have recently been characterized in tissue cultures of cardiac myocytes 7 . An obvious question raised by these observations is whether release of the sequestered Ca 2+ 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 Ca 2+ 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 Ca 2+ 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.