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Title: Effect of Ca/sup 2 +/ overload on phosphoinositide (PI) metabolism in cardiac muscle

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:7246125

The investigated the relationship between Ca/sup 2 +/ load and PI metabolism in isolated rat papillary muscle labeled with (/sup 3/H)inositol. Increase in (Ca/sup 2 +/)/sub o/ from 0-3.6 mM reduced the incorporation of (/sup 3/H) inositol into PI moderately and increased the resting tension slightly. The incorporation of the label into PI was unchanged by 10 ..mu..m A-23187 at 1.8 mM (Ca/sup 2 +/)/sub o/ that increased the contractility by 70% without a significant change in the resting tension. However, either 10.8 mM (Ca/sup 2 +/)/sub o/ or 0.3 mM ouabain at 1.8 mM (Ca/sup 2 +/)/sub o/ markedly decreased the PI labeling with corresponding increase in the resting tension while inclusion of excess EGTA greatly enhanced the radioactivity in PI. Determination of the PI breakdown and the inositol phosphates production by pulse-chase experiments revealed that the reduced PI turnover in the Ca/sup 2 +/-overload muscle was due to both inhibition of the synthesis and stimulation of the breakdown of this lipid that accounted for 30% decrease in the labeled PI from the muscle during 45 min without significant loss of the net PI pool size, suggesting the presence of a relatively smaller compartment of PI pool undergoing a rapid breakdown during Ca/sup 2 +/ overload. The authors propose that alteration of Ca/sup 2 +/ homeostasis may modulate the production of putative second messengers, inositol trisphosphate and diacylglycerol, which feed back to regulate (Ca/sup 2 +/)/sub i/ in cardiac muscle.

Research Organization:
Univ. of Connecticut School of Medicine, Farmington
OSTI ID:
7246125
Report Number(s):
CONF-8606151-; TRN: 86-039172
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
Country of Publication:
United States
Language:
English