Requirement of the inositol trisphosphate receptor for activation of store-operated Ca2+ channels

The coupling mechanism between endoplasmic reticulum (ER) calcium ion (Ca2) stores and plasma membrane (PM) store-operated channels (SOCs) is crucial to Ca2+ signaling but has eluded detection. SOCs may be functionally relat ed to the TRP family of receptor-operated channels. Direct comparison of en dogenous SOCs with stably expressed TRP3 channels in human embryonic kidney (HEK293) cells revealed that TRP3 channels differ in being store independe nt. However, condensed cortical F-actin prevented activation of both SOC an d TRP3 channels, which suggests that ER-PM interactions underlie coupling o f both channels. A cell-permeant inhibitor of inositol trisphosphate recept or (InsP(2)R) function, 2-aminoethoxydiphenyl berate, prevented both recept or-induced TRP3 activation and store-induced SOC activation. It is conclude d that InsP(3)Rs mediate both SOC and TRP channel opening and that the InsP (3)R is essential for maintaining coupling between store emptying and physi ological activation of SOCs.