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The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs. Strathprints provides access to thousands of Open Access research papers by University of Strathclyde researchers, including those from the School of Psychological Sciences & Health - but also papers by researchers based within the Faculties of Science, Engineering, Humanities & Social Sciences, and from the Strathclyde Business School.

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Functionally-separate intracellular ca2+ stores in smooth muscle

Flynn, Elaine R.M. and Bradley, Karen N. and Muir, Thomas C. and McCarron, John G. (2001) Functionally-separate intracellular ca2+ stores in smooth muscle. Journal of Biological Chemistry, 276. pp. 36411-18. ISSN 0021-9258

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Abstract

In smooth muscle, release via the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3R) and ryanodine receptors (RyR) on the sarcoplasmic reticulum (SR) controls oscillatory and steady-state cytosolic Ca2+ concentrations ([Ca2+]c). The interplay between the two receptors, itself determined by their organization on the SR, establishes the time course and spatial arrangement of the Ca2+ signal. Whether or not the receptors are co-localized or distanced from each other on the same store or whether they exist on separate stores will significantly affect the Ca2+ signal produced by the SR. To date these matters remain unresolved. The functional arrangement of the RyR and Ins(1,4,5)P3R on the SR has now been examined in isolated single voltage-clamped colonic myocytes. Depletion of the ryanodine-sensitive store, by repeated application of caffeine, in the presence of ryanodine, abolished the response to Ins(1,4,5)P3, suggesting that Ins(1,4,5)P3R and RyR share a common Ca2+store. Ca2+ release from the Ins(1,4,5)P3R did not activate Ca2+-induced Ca2+ release at the RyR. Depletion of the Ins(1,4,5)P3-sensitive store, by the removal of external Ca2+, on the other hand, caused only a small decrease (∼26%) in caffeine-evoked Ca2+transients, suggesting that not all RyR exist on the common store shared with Ins(1,4,5)P3R. Dependence of the stores on external Ca2+ for replenishment also differed; removal of external Ca2+ depleted the Ins(1,4,5)P3-sensitive store but caused only a slight reduction in caffeine-evoked transients mediated at RyR. Different mechanisms are presumably responsible for the refilling of each store. Refilling of both Ins(1,4,5)P3-sensitive and caffeine-sensitive Ca2+ stores was inhibited by each of the SR Ca2+ ATPase inhibitors thapsigargin and cyclopiazonic acid. These results may be explained by the existence of two functionally distinct Ca2+ stores; the first expressing only RyR and refilled from [Ca2+]c, the second expressing both Ins(1,4,5)P3R and RyR and dependent upon external Ca2+ for refilling.