© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Characterization of a [Ca2+]i-dependent current in human atrial and ventricular cardiomyocytes in the absence of Na+ and K+
Department of Internal Medicine III, University of Cologne, Joseph-Stelzmann-Strasse 9, 50924 Cologne, Germany
* Corresponding author. Tel.: +49-(221)-478-4475; fax: +49-(221)-478-6490.
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+/Ca2+-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 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.
KEYWORDS Human; Arrhythmia (mechanisms); Calcium (cellular); Ion channels; Membrane currents; Membrane permeability
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