BayK 8644 increases resting calcium spark frequency in ferret ventricular myocytes

Heart Vessels. 1997:Suppl 12:58-61.

Abstract

BayK 8644, an L-type Ca2+ channel agonist, has been shown to increase sarcoplasmic reticulum (SR) Ca2+ release in dog and ferret ventricular muscle. The visualization of local increase in cytosolic Ca2+ concentration, called the "Ca2+ spark", has enabled us to investigate the elementary events of the BayK-induced Ca2+ release from the SR. In this study, the effects of BayK on twitch Ca2+ transients and Ca2+ sparks were examined in ferret ventricular myocytes with laser scanning confocal microscopy and a fluorescent calcium indicator, fluo 3. BayK converted the post rest potentiation of twitch Ca2+ transients to decay. The Ca2+ spark frequency under control conditions was fairly constant during 20 s of rest after interruption of electrical stimulation. BayK (100 nM) increased the spark frequency by 465.7 +/- 90.3% of control but did not change the spatial and temporal characteristics of the individual sparks. The increase in spark frequency by BayK was not affected by perfusion with Ca(2+)-free solution, but was suppressed by the addition of nifedipine (10 microM), suggesting that the BayK effects on Ca2+ sparks were mediated by the sarcolemmal dihydropyridine (DHP) receptor, but.were independent of Ca2+ influx. These findings suggest that BayK activates SR Ca2+ release at rest through a putative linkage between the sarcolemmal DHP receptor and the SR ryanodine receptor.

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology*
  • Aniline Compounds
  • Animals
  • Calcium / metabolism*
  • Calcium Channel Agonists / pharmacology*
  • Cells, Cultured
  • Electric Stimulation
  • Ferrets
  • Fluorescent Dyes
  • Heart Ventricles
  • Microscopy, Confocal
  • Myocardial Contraction / drug effects*
  • Myocardial Contraction / physiology
  • Myocardium / cytology
  • Sarcoplasmic Reticulum / metabolism
  • Xanthenes

Substances

  • Aniline Compounds
  • Calcium Channel Agonists
  • Fluorescent Dyes
  • Xanthenes
  • Fluo-3
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Calcium