Role of intracellular Ca2+ and pH in positive inotropic response of cardiomyocytes to diacylglycerol.
Diacylglycerol has been hypothesized to mediate the positive inotropic response of myocardium to the alpha-adrenergic agonists angiotensin II and endothelin. The mechanism of action of diacylglycerol was examined here in adult rat ventricular myocytes by releasing dioctanoylglycerol (diC8) intracellularly from a caged compound while monitoring Ca2+ transients and pH with fluorescent indicators. DiC8 caused a three- to fourfold increase in twitch amplitude and a twofold increase in the systolic Ca2+ transient. No other parameter was consistently influenced by diC8, including the kinetics of Ca2+ cycling, the Ca2+ content of the sarcoplasmic reticulum, or the myofilament Ca2+ sensitivity. DiC8 also had no detectable effect on intracellular pH or Na+/H+ antiport activity. Consistent with this finding, the Na+/H+ exchange inhibitor N-ethylisopropyl amiloride was without effect on the positive inotropic response to diC8. The marked enhancement of systolic Ca2+ by diC8 suggests that the process of excitation-contraction coupling is an important and possibly preferred target of diacylglycerol-protein kinase C signaling in myocardium.
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Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706, USA.
Walker
J W
JW
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002138:Calibration; D002478:Cells, Cultured; D003971:Diastole / Q000187:drug effects; D004075:Diglycerides / Q000494:pharmacology*; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D006352:Heart Ventricles; D006863:Hydrogen-Ion Concentration; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D013050:Spectrometry, Fluorescence / Q000379:methods; D013599:Systole / Q000187:drug effects; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D004075:Diglycerides; D005456:Fluorescent Dyes; C044295:1,2-dioctanoylglycerol; D000584:Amiloride; D002118:Calcium; C039614:ethylisopropylamiloride