Conformational Coupling: a Physiological Calcium Entry Mechanism

The entry of external Ca2+ that is activated by inositol 1,4,5-trisphosphate (IP3) may occur through a conformation coupling mechanism. IP3 receptors in the endoplasmic reticulum located in a junctional zone make contact with entry channels in the plasma membrane. IP3 may act directly to stimulate this coupling complex or IP3 could act indirectly by stimulating uncoupled IP3Rs 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 Ca2+ response to receptor activation may be the stimulation of entry, which is then responsible for charging up the internal store to prime the IP3Rs for the large-scale regenerative release of Ca2+ that occurs during each spike.