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

Hong Tao Ma, Randen L. Patterson, Damian B. Van Rossum, Lutz Birnbaumer, Katsuhiko Mikoshiba, Donald L. Gill

Research output: Contribution to journalArticlepeer-review

535 Scopus citations


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 related to the TRP family of receptor-operated channels. Direct comparison of endogenous SOCs with stably expressed TRP3 channels in human embryonic kidney (HEK293) 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 (InsP3R) function, 2-aminoethoxydiphenyl borate, prevented both receptor-induced TRP3 activation and store-induced SOC activation. It is concluded that InsP3Rs mediate both SOC and TRP channel opening and that the InsP3R is essential for maintaining coupling between store emptying and physiological activation of SOCs.

Original languageEnglish (US)
Pages (from-to)1647-1651
Number of pages5
Issue number5458
StatePublished - Mar 3 2000

All Science Journal Classification (ASJC) codes

  • General


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