Transmission of information from cardiac dihydropyridine receptor to ryanodine receptor: Evidence from BayK 8644 effects on resting Ca2+ sparks

Hideki Katoh, Klaus Schlotthauer, Donald M Bers

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Coupling between L-type Ca2+ channels (dihydropyridine receptors, DHPRS) and ryanodine receptors (RyRs) plays a pivotal role in excitation-contraction (E-C) coupling in cardiac myocytes, and Ca2+ influx is generally accepted as the trigger of sarcoplasmic reticulum (SR) Ca2+ release. The L-type Ca2+ channel agonist BayK 8644 (BayK) has also been reported to alter RyR gating via a functional linkage between DHPR and RyR, independent of Ca2+ influx. Here, the effect of rapid BayK application on resting RyR gating in intact ferret ventricular myocytes was measured as Ca2+ spark frequency (CaSpF) by confocal microscopy and fluo 3. BayK increased resting CaSpF by 401 ± 15% within 10 seconds in Ca2+-free solution, and depolarization had no additional effect. The effect of BayK on CaSpF was dose-dependent, but even 50 nmol/L BayK induced a rapid 245 ± 12% increase in CaSpF. Nifedipine (5 μmol/L) had no effect by itself on CaSpF, but it abolished the BayK effect (presumably by competitive inhibition at the DHPR). The nondihydropyridine Ca2+ channel agonist FPL-64176 (1 μmol/L) did not alter CaSpF (despite rapid and potent enhancement of Ca2+ current, I(Ca)). In striking contrast to the very rapid and depolarization-independent effect of BayK on CaSpF, BayK increased I(Ca) only slowly (τ= 18 seconds), and the effect was greatly accelerated by depolarization. We conclude that in ferret ventricular myocytes, BayK effects on I(Ca) and CaSpF both require drag binding to the DHPR, but postreceptor pathways may diverge in transmission to the gating of the L-type Ca2+ channel and RyR.

Original languageEnglish (US)
Pages (from-to)106-111
Number of pages6
JournalCirculation Research
Volume87
Issue number2
StatePublished - Jul 21 2000
Externally publishedYes

Keywords

  • Ca channel
  • Confocal microscopy
  • Excitation-contraction coupling
  • FPL-64176
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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