‘Quanta’ Ca2+ release and the control of Ca2+ entry by inositol phosphates ‐ a possible mechanism

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Abstract
The release of Ca2+ from intracellular stores by sub‐optimal doses of inositol trisphosphate has been shown to be dose‐related (‘quantal’), and a simple model is proposed here to account for this phenomenon. It is suggested that there is a regulatory Ca2+‐binding site on, or associated with, the luminal domain of the InsP3 receptor, which allosterically controls Ca2+ efflux, and the affinity for Ca2+ of that site is modulated by InsP3 binding to the cytoplasmic domain of the receptor; a similar mechanism applied to the ryanodine receptor might also explain some aspects of Ca2+ ‐induced Ca2+ release. The stimulated entry of Ca2+ into a cell which occurs upon activation of inositide‐linked receptors has been variously and confusingly proposed to be regulated by InsP3, InsP4, and/or a ‘capacitative’ Ca2+ pool; the mechanism of InsP, receptor action suggested here is shown to lead to a potential reconciliation of all these conflicting proposals.