Ins(1,4,5)P3 receptor regulation during 'quantal' Ca2+ release in smooth muscle

Abstract

Smooth muscle is activated by plasma-membrane-acting agonists that induce inositol (1,4,5)-trisphosphate [Ins(1,4,5)P(3)] to release Ca(2+) from the intracellular sarcoplasmic reticulum (SR) Ca(2+) store. Increased concentrations of agonist evoke a concentration-dependent graded release of Ca(2+) in a process called 'quantal' Ca(2+) release. Such a graded release seems to be incompatible with both the finite capacity of the SR store and the positive-feedback Ca(2+)-induced Ca(2+) release (CICR)-like process that is operative at Ins(1,4,5)P(3) receptors, which - once activated - might be expected to deplete the entire store. Proposed explanations of quantal release include the existence of multiple stores, each with different sensitivities to Ins(1,4,5)P(3), or Ins(1,4,5)P(3) receptor opening being controlled by the Ca(2+) concentration within the SR. Here, we suggest that the regulation of Ins(1,4,5)P(3) receptors by the Ca(2+) concentration within the SR explains the quantal Ca(2+)-release process and the apparent existence of multiple Ca(2+) stores in smooth muscle.