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

Olaf F. Köster, Gyula P. Szigeti, Dirk J. Beuckelmann

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Objectives: In situations of [Ca2+](i) overload, arrhythmias are believed to be triggered by delayed after depolarizations, which are generated by a transient inward current I(TI). This study was designed to examine [Ca2+](i)-dependent membrane currents in the absence of the Na+/Ca2+-exchanger as possible contributors to I(TI) 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)-measurements were performed using 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 [Ca-2+](i)-dependent chloride channel seems to be expressed. Possible delayed after depolarizations in human ventricular myocardium might therefore be carried by the Na+/Ca2+- exchanger alone.

Original languageEnglish
Pages (from-to)175-187
Number of pages13
JournalCardiovascular research
Volume41
Issue number1
DOIs
Publication statusPublished - Jan 1 1999

Keywords

  • Arrhythmia (mechanisms)
  • Calcium (cellular)
  • Human
  • Ion channels
  • Membrane currents
  • Membrane permeability

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Characterization of a [Ca<sup>2+</sup>]-dependent current in human atrial and ventricular cardiomyocytes in the absence of Na<sup>+</sup> and K<sup>+</sup>'. Together they form a unique fingerprint.

  • Cite this