pH dependence of inositol 1,4,5-trisphosphate-induced Ca2+ release in permeabilized smooth muscle cells of the guinea-pig

J Physiol. 1994 Mar 15;475(3):369-75. doi: 10.1113/jphysiol.1994.sp020078.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cell Membrane Permeability
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Hydrogen-Ion Concentration*
  • Inositol 1,4,5-Trisphosphate / pharmacology*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism*
  • Osmolar Concentration
  • Time Factors

Substances

  • Inositol 1,4,5-Trisphosphate
  • Calcium