Spontaneous calcium release from inositol trisphosphate-sensitive calcium stores

Abstract

Inositol 1,4,5-trisphosphate (InsP₃) functions as a second messenger to mobilize Ca²⁺ from intracellular reservoirs¹. The release mechanism displays all-or-none characteristics^2,3, that may account for other observations that the InsP₃-induced mobilization of Ca²⁺ is quantal^4–6. Quantal release may depend on the sensitivity of the InsP₃ receptor being regulated by the Ca²⁺ concentration in the lumen of the endoplasmic reticulum⁷. We report here that the InsP₃-sensitive store in hepatocytes discharges spontaneously when overloaded with Ca²⁺. The release, which is blocked by heparin, is preceded by an increasing sensitivity of the InsP₃ receptor to endogenous InsP₃, and is promoted by those sulphydryl reagents (oxidized glutathione and thimerosal) that induce Ca²⁺ oscillations in intact cells (ref. 8, and T. A. Rooney, D. C. Renard, E. J. Sass and A. P. Thomas, manuscript in preparation). This novel process could have a role in generating both Ca²⁺ oscillations and Ca²⁺ waves.