Effects of endothelin-1 on calcium and potassium currents in undiseased human ventricular myocytes

J. Magyar, N. Iost, Á Körtvély, T. Bányász, L. Virág, P. Szigligeti, A. Varró, M. Opincariu, J. Szécsi, J. G. Papp, P. P. Nánási

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Abstract

Endothelins have been reported to exert a wide range of electrophysiological effects in mammalian cardiac cells. These results are controversial and human data are not available. Our aim was to study the effects of endothelin-1 (ET-1, 8 nmol/l) on the L-type calcium current (ICa-L) and various potassium currents (rapid component of the delayed rectifier, IKr; transient outward current, Ito; and the inward rectifier K current, IK1) in isolated human ventricular cardiomyocytes. Cells were obtained from undiseased donor hearts using collagenase digestion via the segment perfusion technique. The whole-cell configuration of the patch-clamp technique was applied to measure ionic currents at 37°C. ET-1 significantly decreased peak ICa-L from 10.2±0.6 to 6.8±0.8 pA/pF at +5 mV (66.7% of control, P<0.05, n=5). This reduction of peak current was accompanied by a lengthening of inactivation. The voltage dependence of steady-state activation and inactivation was not altered by ET-1. IKr, measured as tail current amplitudes at -40 mV, decreased from 0.31±0.02 to 0.06±0.02 pA/pF (20.3% of control, P<0.05, n=4) after exposure to ET-1. ET-1 failed to change the peak amplitude of Ito, measured at +50 mV (9.3±4.6 and 9.0±4.4 pA/pF before and after ET-1, respectively), or steady-state IK1 amplitude, measured at the end of a 400-ms hyperpolarization to -100 mV (3.6±1.4 and 3.7±1.4 pA/pF, n=4). The present results indicate that in undiseased human ventricular myocytes ET-1 inhibits both ICa-L and IKr; however, the degree of suppression of the two currents is different.

Original languageEnglish
Pages (from-to)144-149
Number of pages6
JournalPflugers Archiv European Journal of Physiology
Volume441
Issue number1
DOIs
Publication statusPublished - Dec 1 2000

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Keywords

  • Action potentials
  • Calcium currents
  • Cardiac cells
  • Endothelins
  • Human myocytes
  • Potassium currents

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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