Effect of Ca/sup 2 +/ overload on phosphoinositide (PI) metabolism in cardiac muscle
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
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Related Subjects
CALCIUM COMPOUNDS
BIOLOGICAL EFFECTS
PHOSPHOLIPIDS
METABOLISM
CATIONS
HOMEOSTASIS
INOSITOL
MUSCLES
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALINE EARTH METAL COMPOUNDS
ANIMALS
CARBOHYDRATES
CHARGED PARTICLES
ESTERS
INOSITOLS
IONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPIDS
MAMMALS
MONOSACCHARIDES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
RODENTS
SACCHARIDES
VERTEBRATES
550501* - Metabolism- Tracer Techniques