Conformational Coupling: A Physiological Calcium Entry Mechanism

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Abstract
The entry of external Ca 2+ that is activated by inositol 1,4,5-trisphosphate (IP 3 ) may occur through a conformation coupling mechanism. IP 3 receptors in the endoplasmic reticulum located in a junctional zone make contact with entry channels in the plasma membrane. IP 3 may act directly to stimulate this coupling complex or IP 3 could act indirectly by stimulating uncoupled IP 3 Rs in the vicinity of the junctional zone to induce a localized depletion of the ER store to switch on a store-operated mechanism. At physiological agonist concentrations, the earliest Ca 2+ response to receptor activation may be the stimulation of entry, which is then responsible for charging up the internal store to prime the IP 3 Rs for the large-scale regenerative release of Ca 2+ that occurs during each spike.