Different effects of endothelin-1 on calcium and potassium currents in canine ventricular cells

T. Bányász, J. Magyar, Á Körtvély, G. Szigeti, P. Szigligeti, Z. Papp, Attila Mohácsi, L. Kovács, P. P. Nánási

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Abstract

Effects of endothelin-1 (ET-1) on the L-type calcium current (ICa) and delayed rectifier potassium current (IK) were studied in isolated canine ventricular cardiomyocytes using the whole-cell configuration of the patch-clamp technique. ET-1 (8 nM) was applied in three experimental arrangements: untreated cells, in the presence of 50 nM isoproterenol, and in the presence of 250 μM 8-bromo-cAMP. In untreated cells, ET-1 significantly decreased the peak amplitude of ICa by 32.3±4.8% at +5 mV P<0.05 without changing activation or inactivation characteristics of ICa. ET-1 had no effect on the amplitude of IK, Ito (transient outward current) or IK1 (inward rectifier K current) in untreated cells; however, the time course of recovery from inactivation of Ito was significantly increased by ET-1 (from 26.5±4.6 ms to 59.5±1.8 ms, P<0.05). Amplitude and time course of intracellular calcium transients, recorded in voltage-clamped cells previously loaded with the fluorescent calcium indicator dye Fura-2, were not affected by ET-1. ET-1 had no effect on force of contraction in canine ventricular trabeculae. Isoproterenol increased the amplitude of ICa to 263±29% of control. ET-1 reduced ICa also in isoproterenol-treated cells by 17.8±2% (P<0.05); this inhibition was significantly less than obtained in untreated cells. IK was increased by isoproterenol to 213±18% of control. This effect of isoproterenol on IK was reduced by 31.8±4.8% if the cells were pretreated with ET-1. Similarly, in isoproterenol-treated cells ET-1 decreased IK by 16.2±1.5% (P<0.05). Maximal activation of protein kinase A (PKA) was achieved by application of 8-bromo-cAMP in the pipette solution. In the presence of 8-bromo-cAMP ET-1 failed to alter ICa or IK. It was concluded that differences)in effects of ET-1 on ICa and IK may be related to differences in cAMP sensitivity of the currents.

Original languageEnglish
Pages (from-to)383-390
Number of pages8
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume363
Issue number4
DOIs
Publication statusPublished - Jan 1 2001

Keywords

  • Action potential
  • Calcium current
  • Cardiac cells
  • Endothelin
  • Potassium currents
  • Signal transduction
  • cAMP

ASJC Scopus subject areas

  • Pharmacology

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