Possible functional linkage between the cardiac dihydropyridine and ryanodine receptor: Acceleration of rest decay by Bay K 8644

E. McCall, L. V. Hryshko, V. M. Stiffel, D. M. Christensen, Donald M Bers

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

The effect of the dihydropyridine L-Type Ca chanel agonist Bay K 8644 on post-rest contractions in ferret ventricular muscle and isolated myocytes was investigated. Bay K 8644 was shown to abolish rest potentiation and greatly accelerate rest decay. The post-rest contraction suppressed by Bay K 8644 was accompanied by action potentials of large amplitude and longer duration, but voltage-clamp measurements showed that this suppression was not due to a supra-optimal I(Ca) trigger. Caffeine-induced contractures and rapid cooling contractures demonstrated an accelerated rest-dependent decline in sarcoplasmic reticulum (SR) Ca content in the presence of Bay K 8644, which was present even with Ca-free superfusion during rest. Thus, the Bay K 8644-induced decline of SR Ca during rest was independent of extracellular Ca or I(Ca). To explore whether the binding of Bay K 8644 to the dihydropyridine receptor could alter the SR Ca release channel/ryanodine receptor in a more direct way, ryanodine binding was measured in the absence and presence of Bay K 8644. Ryanodine binding to isolated ferret ventricular myocytes was increased by Bay K 8644 under conditions where sarcolemmal-SR junctions might be expected to be intact, but not after physical disruption. These results are consistent with a working hypothesis where Bay K 8644 may bind to the dihydropyridine receptor and this may lead to physical changes in the linkage between the dihydropridine receptor and a subset of ryanodine receptors, thereby increasing the opening of the SR Ca release channel during rest (and accelerating resting Ca loss).

Original languageEnglish (US)
Pages (from-to)79-93
Number of pages15
JournalJournal of Molecular and Cellular Cardiology
Volume28
Issue number1
DOIs
StatePublished - Jan 8 1996
Externally publishedYes

Keywords

  • Bay K 8644
  • Cardiac muscle
  • Dihydropyridine receptor
  • Ryanodine receptor
  • Sarcolemmal Ca channel
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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