Effect of calcium overload on the phosphoinositide breakdown in the rat left ventricular papillary muscle |
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Authors: | Hajime Otani Hitomi Otan Masao Morita Dipak K Das |
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Institution: | (1) Department of Thoracic Surgery, Kansai Medical University, 570 Osaka, Japan;(2) Department of Pharmacology, Kansai Medical University, 570 Osaka, Japan;(3) Cardiovascular Division, Department of Surgery, University of Connecticut, School of Medicine, 06032 Farmington, Connecticut, USA;(4) Department of Surgery, Cardiovascular Division, University of Connecticut, School of Medicine, 06032 Farmington, Connecticut, USA |
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Abstract: | We investigated the effect of Ca2+ overload on the phospholipase C-catalyzed hydrolysis of phosphoinositides in the rat left ventricular papillary muscle. Ca2+ overload on the papillary muscle was induced by treatment with 0.3 mM ouabain in Ca2+-containing medium following either Ca2+-containing or Ca2+-free superfusion. The phosphoinositide breakdown was evaluated by determining accumulations of 3H]inositol phosphates (3H]IPs) in the tissues prelabeled with 3H]inositol. Ca2+ repletion following Ca2+-free superfusion resulted in a rapid but small increase in resting tension that was not followed by contracture, nor was it associated with a significant increase in 3H]IPs accumulations. Treatment with ouabain following Ca2+-containing superfusion increased resting tension after a lag period of several minutes and produced contracture associated with an increase in 3H]IPs accumulations. The ouabain induced increases in resting tension, and accumulations of 3H]IPs were significantly potentiated by prior Ca2+-free superfusion instead of Ca2+-containing superfusion. There was a significant positive correlation between increases in resting tension and the phosphoinositide breakdown. The increased resting tension and the accumulations of 3H]IPs were not antagonized by treatments with prazosin plus atropine or indomethacin, but were abolished by superfusion with Ca2+-free buffer solution. Although the enhanced phospholipase C-catalyzed hydrolysis of phosphoinositides appears to be a consequence rather than a cause of increased intracellular Ca2+, such a biochemical change may provoke a positive feedback mechanism to develop the muscle contracture through the putative intracellular messenger action of inositol triphosphate and diacylglycerol.Abbreviations 3H]IPs
3H]Inositol Phosphates
- IP
Inositol Phosphate
- IP2
Inositol Bisphosphate
- IP3
Inositol Trisphosphate
- PI
Phosphatidylinositol
- PI-4-P
Phosphatidylinositol-4-phosphate
- PI-4,5-P2
Phosphatidylinositol 4,5-bisphosphate
- PRZ
Prazosin
- ATR
Atropine
- INDO
Indomethacin
- min
Minutes |
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Keywords: | papillary muscle calcium overload calcium paradox phosphoinositide breakdown |
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