Gating of Store-Operated Channels by Conformational Coupling to Ryanodine Receptors

We report here that RyRs interact with and gate the store-operated hTrp3 and I crac channels. This gating contributes to activation of hTrp3 and I crac by agonists. Coupling of hTrp3 to IP 3Rs or RyRs in the same cells was found to be mutually exclusive. Biochemical and functional evidence suggest that mutually exclusive coupling reflects clustering and segregation of hTrp3-IP 3R and hTrp3-RyR complexes in plasma membrane microdomains. Gating of CCE by RyRs indicates that gating by conformational coupling is not unique to skeletal muscle but is a general mechanism for communication between events in the plasma and endoplasmic reticulum membranes.