Effects of β-adrenoceptor stimulation on delayed rectifier K + currents in canine ventricular cardiomyocytes

G. Harmati, T. Bányász, L. Bárándi, N. Szentandrássy, B. Horváth, G. Szabõ, J. A. Szentmiklõsi, G. Szénási, P. P. Nánási, J. Magyar

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Abstract

Background and Purpose While the slow delayed rectifier K + current (I Ks) is known to be enhanced by the stimulation of β-adrenoceptors in several mammalian species, phosphorylation-dependent regulation of the rapid delayed rectifier K + current (I Kr) is controversial. Experimental Approach In the present study, therefore, the effect of isoprenaline (ISO), activators and inhibitors of the protein kinase A (PKA) pathway on I Kr and I Ks was studied in canine ventricular myocytes using the whole cell patch clamp technique. Key Results I Kr was significantly increased (by 30-50%) following superfusion with ISO, forskolin or intracellular application of PKA activator cAMP analogues (cAMP, 8-Br-cAMP, 6-Bnz-cAMP). Inhibition of PKA by Rp-8-Br-cAMP had no effect on baseline I Kr. The stimulating effect of ISO on I Kr was completely inhibited by selective β 1-adrenoceptor antagonists (metoprolol and CGP-20712A), by the PKA inhibitor Rp-8-Br-cAMP and by the PKA activator cAMP analogues, but not by the EPAC activator 8-pCPT-2'-O-Me-cAMP. In comparison, I Ks was increased threefold by the activation of PKA (by ISO or 8-Br-cAMP), and strongly reduced by the PKA inhibitor Rp-8-Br-cAMP. The ISO-induced enhancement of I Ks was decreased by Rp-8-Br-cAMP and completely inhibited by 8-Br-cAMP. Conclusions and Implications The results indicate that the stimulation of β 1-adrenoceptors increases I Kr, similar to I Ks, via the activation of PKA in canine ventricular cells.

Original languageEnglish
Pages (from-to)890-896
Number of pages7
JournalBritish journal of pharmacology
Volume162
Issue number4
DOIs
Publication statusPublished - Feb 1 2011

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Keywords

  • I
  • I
  • PKA
  • cAMP
  • delayed rectifier K current
  • dog myocytes
  • isoprenaline
  • β-adrenoceptors

ASJC Scopus subject areas

  • Pharmacology

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