Heterogeneity of channel density in inositol-1,4,5-trisphosphate-sensitive Ca(2positive) stores

Inositol-1,4,5-trisphosphate (InsP3)-induced Ca2+ release is a key mechanism for intracellular Ca2+ mobilization. The rate of Ca2+ release declines progressively with time until a higher concentration of InsP3 is added, which is referred to as the incremental detection mechanism. Two hypotheses have...

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Bibliographic Details
Published inNature (London) Vol. 372; no. 6508; pp. 791 - 794
Main Authors Hirose, Kenzo, Iino, Masamitsu
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group 22.12.1994
Subjects
Calcium
Cellular biology
Heterogeneity
Kinetics
Pharmacology
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Summary:Inositol-1,4,5-trisphosphate (InsP3)-induced Ca2+ release is a key mechanism for intracellular Ca2+ mobilization. The rate of Ca2+ release declines progressively with time until a higher concentration of InsP3 is added, which is referred to as the incremental detection mechanism. Two hypotheses have been postulated to explain these complex kinetics: (1) Ca2+ stores consist of multiple compartments (quanta) with different sensitivities to InsP3 (refs 3-7), and (2) the rate of Ca2+ release is modulated by the Ca2+ concentration in the lumen of Ca2+ stores. We studied this phenomenon by real-time measurement of the luminal Ca2+ concentration of Ca2+ stores using a Ca(2+)-sensitive fluorescent dye, but our results were not explained by either of these hypotheses. Here we report that the complex kinetics of Ca2+ release results from the heterogeneous density of equally InsP3-sensitive channels on the Ca2+ stores. This heterogeneity creates Ca2+ stores with apparently different sensitivities to InsP3, which may have different functions in Ca2+ mobilization.
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ISSN:0028-0836
1476-4687
DOI:10.1038/372791a0