BAY K 8644 depresses excitation-contraction coupling in cardiac muscle.
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 (ICa) 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 ICa and SR Ca load, the contraction elicited was much smaller in the presence of BAY. BAY also induced a characteristic negative shift in the 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.
McCall
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Department of Physiology, Loyola University Medical Center, Maywood, Illinois 60152, USA.
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004558:Electric Stimulation; D005289:Ferrets; D006352:Heart Ventricles; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013997:Time Factors
D013757:Tetraethylammonium Compounds; D002110:Caffeine; D019789:Tetraethylammonium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium