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 1083-351XFull text not available in this repository. (Request a copy from the Strathclyde author)
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.
|Keywords:||sarcoplasmic reticulum, Ca2+ concentrations, receptors, intracellular Ca2+ store, smooth muscle, Pharmacy and materia medica, Biochemistry, Cell Biology, Molecular Biology|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Pure Administrator|
|Date Deposited:||13 Feb 2012 11:19|
|Last modified:||22 Mar 2017 09:56|