Cyclic-AMP-dependent phosphorylation modulates the stereospecific activation of cardiac Ca channels by Bay K 8644

F. Tiaho, S. Richard, P. Lory, J. M. Nerbonne, J. Nargeot

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Voltage-gated Ca channels have been reported to be regulated by membrane potential, phosphorylation and binding of specific agonists or antagonists such as dihydropyridines. We report here evidence that cyclic AMP (cAMP) modulates the activation of Ca-channel current by the dihydropyridine agonist Bay K 8644. Bay K 8644 (racemate) alone induces a primary voltage-dependent, potentiating effect on peak current amplitude and accelerates the current decay. In contrast, in the presence of cAMP activators, we observed a striking slowing of the decay in addition to the increase in peak current. The agonist (-)-Bay K 8644, but not the antagonist (+)-Bay K 8644, when applied in combination with cAMP, forskolin or isoproterenol, mimics the effect of the racemate. We have interpreted the results presented here in respect of a cAMP-dependent modulation of Bay K 8644 effects on cardiac Ca-channel currents. It may open the new perspective that dephosphorylated and phosphorylated Ca channels have distinct pharmacology.

Original languageEnglish
Pages (from-to)58-66
Number of pages9
JournalPflügers Archiv European Journal of Physiology
Volume417
Issue number1
DOIs
StatePublished - Sep 1 1990
Externally publishedYes

Keywords

  • Ca channel current
  • Dihydropyridine agonist Bay K 8644
  • Stereospecific interaction
  • cAMP-dependent modulation

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