The kinetics of Ins(1,4,5)P3 (InsP3)-stimulated Ca2+ release from intracellular stores are unusual in that submaximal concentrations of InsP3 rapidly release only a fraction of the InsP3-sensitive Ca2+ stores. By measuring unidirectional 45Ca2+ efflux from permeabilized rat hepatocytes, we demonstrate that such quantal responses to InsP3 occur at all temperatures between 2 and 37 °C, but at much lower rates at the lower temperatures. Preincubation with submaximal concentrations of InsP3, which themselves evoked quantal Ca2+ release, had no effect on the sensitivity of the stores to further additions of InsP3. The final Ca2+ content of the stores was the same whether they were stimulated with two submaximal doses of InsP3 or a single addition of the sum of these doses. Such incremental responses and the persistence of quantal behaviour at 2 °C indicate that InsP3-evoked receptor inactivation is unlikely to be the cause of quantal Ca2+ mobilization. Reducing the Ca2+ content of the intracellular stores by up to 45% did not affect their sensitivity to InsP3, but substantially reduced the time taken for each submaximal InsP3 concentration to exert its full effect. These results suggest that neither luminal nor cytosolic Ca2+ regulation of InsP3 receptors are the determinants of quantal behaviour. Our results are not therefore consistent with incremental responses to InsP3 depending on mechanisms involving attenuation of InsP3 receptor function by cytosolic or luminal Ca2+ or by InsP3 binding itself. We conclude that incremental activation of Ca2+ release results from all-or-nothing emptying of stores with heterogeneous sensitivities to InsP3. These characteristics allow rapid graded recruitment of InsP3-sensitive Ca2+ stores as the cytosolic InsP3 concentration increases.
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August 1997
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Research Article|
August 15 1997
Incremental Ca2+ mobilization by inositol trisphosphate receptors is unlikely to be mediated by their desensitization or regulation by luminal or cytosolic Ca2+
Mike D. BEECROFT;
Mike D. BEECROFT
1Department of Pharmacology, Tennis Court Road, Cambridge CB2 1QJ, U.K.
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Colin W. TAYLOR
Colin W. TAYLOR
1
1Department of Pharmacology, Tennis Court Road, Cambridge CB2 1QJ, U.K.
1To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Received:
January 23 1997
Revision Received:
April 04 1997
Accepted:
April 18 1997
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1997
1997
Biochem J (1997) 326 (1): 215–220.
Article history
Received:
January 23 1997
Revision Received:
April 04 1997
Accepted:
April 18 1997
Citation
Mike D. BEECROFT, Colin W. TAYLOR; Incremental Ca2+ mobilization by inositol trisphosphate receptors is unlikely to be mediated by their desensitization or regulation by luminal or cytosolic Ca2+. Biochem J 15 August 1997; 326 (1): 215–220. doi: https://doi.org/10.1042/bj3260215
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