Characterization of a [Ca2+]i-dependent current in human atrial and ventricular cardiomyocytes in the absence of Na+ and K+

Objectives: In situations of [Ca2+](i)-overload, arrhythmias are believed to be triggered by delayed afterdepolarizations, which are generated by a transient inward current I-Tl. This study was designed to examine [Ca2+](i)-dependent membrane currents in the absence of the Na+/Ca2+-exchanger as possible contributors to I-Tl in human cardiac cells. Methods: The whole cell voltage clamp technique was used for electrophysiological measurements in human atrial and ventricular cardiomyocytes. [Ca2+](i)-measurements were performed using the fluorescent Ca2+-indicator fura-2. All solutions were Na+-free. Voltage-independent [Ca2+](i)-transients were elicited by rapid caffeine applications. Results: In atrial myocytes, caffeine induced a transient membrane current in the absence of Na+ and K+. This current could be suppressed by internal EGTA (10 mM). Cl- did not contribute to this current. Experiments with different cations suggested non-selectivity for Cs+ and Li+, whereas N-methyl-D-glucamine appeared to be impermeable. Voltage ramps indicated a linear current-voltage relation in the range of +80 to -80 mV. Fluorescence measurements revealed a dissociation between the time courses of current and bulk [Ca2+](i)-signal. In ventricular cardiomyocytes, caffeine failed to induce transient currents in 54 cells from 22 different patients with or without terminal heart failure. Conclusions: In human atrial cardiomyocytes, a [Ca2+](i)-dependent nonspecific cation channel is expressed and may contribute to triggered arrhythmias in situations of [Ca2+](i)-overload. No evidence could be found for the existence of a [Ca2+](i)-dependent chloride current in atrial cells. In ventricular cells, neither a [Ca2+](i)-dependent nonspecific cation channel nor a [Ca2+](i)-dependent chloride channel seems to be expressed. Possible delayed afterdepolarizations in human ventricular myocardium might therefore be carried by the Na+/Ca2+-exchanger alone. (C) 1999 Elsevier Science B.V. All rights reserved.