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

ABSTRACT

OBJECTIVES: In situations of [Ca2+]i-overload, arrhythmias are believed to be triggered by delayed afterdepolarizations, which are generated by a transient inward current ITI. This study was designed to examine [Ca2+]i-dependent membrane currents in the absence of the Na+/Ca(2+)-exchanger as possible contributors to ITI 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 Ca(2+)-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+/Ca(2+)-exchanger alone.