Purified Reconstituted Inositol 1,4,5-Trisphosphate Receptors

Thimerosal, a sulfhydryl oxidizing reagent, has been shown to induce Ca2+ mobilization in several cell types and to increase the sensitivity of intracellular Ca2+ stores to inositol 1,4,54risphosphate (IP,). Using purified IP, receptor (IP,R) protein reconstituted in vesicles, we demonstrate pronounced stimulation by thimerosal of its Ca2+ channel activity. Effects of thimerosal are dependent on the redox state of the receptor, implying an action of thimerosal on a critical sulfhydryl group(s) of IP,R. Thimerosal enhances the affinity of IP,R for IP, binding. The manner in which thimerosal modulates IP,R responsiveness to IP, provides evidence for receptor heterogeneity with implications for mechanisms of quantal Ca2+ release. These results clarify regulation of IP,R activity by redox modulation.