Requirement of the Inositol Trisphosphate Receptor for Activation of Store-Operated [Ca.sup.2+] Channels

Receptor-induced [Ca.sup.2+] signals comprise two interdependent components--rapid [Ca.sup.2+] release from [Ca.sup.2+] stores in the ER and [Ca.sup.2+] entry through slowly activating PM SOCs. The trigger for SOC activation is decreased [...]
The coupling mechanism between endoplasmic reticulum (ER) calcium ion ([Ca.sup.2+]) stores and plasma membrane (PM) store-operated channels (SOCs) is crucial to [Ca.sup.2+] signaling but has eluded detection. SOCs may be functionally related to the TRP family of receptor-operated channels. Direct comparison of endogenous SOCs with stably expressed TRP3 channels in human embryonic kidney (HEK2933 cells revealed that TRP3 channels differ in being store independent. However, condensed cortical F-actin prevented activation of both SOC and TRP3 channels, which suggests that ER-PM interactions underlie coupling of both channels. A cell-permeant inhibitor of inositol trisphosphate receptor (Ins[P.sub.3]R) function, 2-aminoethoxydiphenyl borate, prevented both receptor-induced TRP3 activation and store-induced SOC activation. It is concluded that Ins[P.sub.3]Rs mediate both SOC and TRP channel opening and that the Ins[P.sub.3]R is essential for maintaining coupling between store emptying and physiological activation of SOCs.