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Allosteric regulation by cytoplasmic Ca 2+ and IP 3 of the gating of IP 3 receptors in permeabilized guinea‐pig vascular smooth muscle cells
Author(s) -
Hirose Kenzo,
Kadowaki Shiro,
Iino Masamitsu
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.407bw.x
Subject(s) - egta , inositol , allosteric regulation , receptor , biophysics , chemistry , vascular smooth muscle , calcium , inositol phosphate , biochemistry , biology , endocrinology , smooth muscle , organic chemistry
1 The potentiation by Ca 2+ of inositol 1,4,5‐trisphosphate (IP 3 )‐induced Ca 2+ release was studied by measuring luminal Ca 2+ concentrations of the Ca 2+ stores using a fluorescent Ca 2+ indicator, furaptra, in permeabilized smooth muscle cells. 2 Ca 2+ release at 10 μM IP 3 was potentiated by an increase in the cytoplasmic Ca 2+ concentration in the presence of 10 mM EGTA. This effect was not due to the pharmacological effect of EGTA, because changes in the EGTA concentration at a constant Ca 2+ concentration had no effect on the Ca 2+ release rate. 3 With an increase in the cytoplasmic Ca 2+ concentration from 30 to 630 nM, the Ca 2+ release rate at a saturating IP 3 concentration increased 110‐fold and the EC 50 for IP 3 increased from 0.07 to 1.0 μM. It was also indicated that the relationship between Ca 2+ concentration and Ca 2+ release rate was shifted towards higher Ca 2+ concentrations at higher IP 3 concentrations. 4 These results suggest that IP 3 and submicromolar concentrations of Ca 2+ allosterically lower the affinity of the IP 3 receptor for each other and are both required for IP 3 receptor activation. These properties enable the IP 3 receptors to detect simultaneous increases in IP 3 and Ca 2+ concentrations.