BAY K 8644 depresses excitation-contraction coupling in cardiac muscle

E. Mccall, Donald M Bers

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

We determined the effect of the dihydropyridine L-type Ca channel agonist BAY K 8644 (BAY) on excitation-contraction (E-C) coupling in isolated ferret ventricular myocytes using whole cell voltage clamp. The sarcoplasmic reticulum (SR) Ca load during the test pulses, assessed by caffeine-induced contractures, was similar in the presence and absence of BAY, with extracellular Ca concentration lowered from 3 to 1 mM in BAY. The relationship between L-type Ca current (I(Ca)) and contraction was assessed, with current and contractions measured during depolarizations from -40 to between -30 and +50 mV after a conditioning train (to ensure constant SR Ca load). BAY shifted the current-contraction relationship downward, such that, for a given I(Ca) and SR Ca load, the contraction elicited was much smaller in the presence of BAY. BAY also induced a characteristic negative shift in the current-voltage relationship. We conclude that BAY decreases the efficacy of a given Ca current to induce SR Ca release during E-C coupling in ferret cardiac tissue (in contrast to the BAY-induced increase of resting SR Ca release). This may reflect an alteration in the state of the SR Ca release channel due to BAY binding to dihydropyridine receptors.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume270
Issue number3 39-3
StatePublished - Mar 1996
Externally publishedYes

Keywords

  • calcium current
  • dihydropyridine
  • ferret ventricular myocytes
  • sarcoplasmic reticulum

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

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