Gating of store-operated channels by conformational coupling to ryanodine receptors

We report here that RyRs interact with and gate the store-operated hTrp3 an d I-crac channels. This gating contributes to activation of hTrpS and I-cra c by agonists. Coupling of hTrp3 to IP(3)Rs or RyRs in the same cells was f ound to be mutually exclusive. Biochemical and functional evidence suggest that mutually exclusive coupling reflects clustering and segregation of hTr p3-RyR and hTrp3-RyR complexes in plasma membrane microdomains. Gating of C CE by RyRs indicates that gating by conformational coupling is not unique t o skeletal muscle but is a general mechanism for communication between even ts in the plasma and endoplasmic reticulum membranes.