pH dependence of inositol 1,4,5-trisphosphate-induced Ca2+ release in permeabilized smooth muscle cells of the guinea-pig.
1. The dependence on pH of inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release was studied in saponin-skinned smooth muscle cells from guinea-pig portal vein, using the indicator fura-2 to monitor Ca2+ release. 2. Increasing pH between 6.7 and 7.3 enhanced the rate of IP3-induced Ca2+ release at all the Ca2+ concentrations above 30 nM without changing the bell-shaped dependence of the Ca2+ release rate on Ca2+ concentration with a peak near 300 nM. 3. The ascending limb of the biphasic Ca2+ dependence was shifted slightly toward the lower Ca2+ concentration at pH 7.3, suggesting an increase in the Ca2+ sensitivity of IP3-induced Ca2+ release at the higher pH. 4. With the elevation in pH from 6.7 to 7.3 at 100 nM Ca2+, about 7-fold higher IP3 concentration was required to release half of the Ca2+ in the store within 15 s. This pH-dependent change in the IP3 sensitivity was smaller at 1 microM Ca2+ and was indiscernible in the absence of Ca2+. 5. These results suggest that H+ may inhibit binding of IP3 and Ca2+ to the modulator sites of the Ca2+ release mechanism. However, these effects on the binding sites may not fully explain the complex effect of pH, and there may be pH-dependent step(s) involved in the gating mechanism of IP3 channels. The present study demonstrates the importance of pH as a modulator of IP3-induced Ca2+ release.
Tsukioka
M
M
Department of Pharmacology, Faculty of Medicine, University of Tokyo, Japan.
Iino
M
M
Endo
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D013997:Time Factors
D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium