Heterogeneity of channel density in inositol-1,4,5-trisphosphate-sensitive Ca2+ 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 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.
Hirose
K
K
Department of Pharmacology, Faculty of Medicine, University of Tokyo, Japan.
Iino
M
M
D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002451:Cell Compartmentation; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010080:Oxazoles; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism
D001572:Benzofurans; D015220:Calcium Channels; D005456:Fluorescent Dyes; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010080:Oxazoles; D018160:Receptors, Cytoplasmic and Nuclear; C058776:2-(2-(5-carboxy)oxazole)-5-hydroxy-6-aminobenzofuran-N,N,O-triacetic acid; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D016257:Fura-2