Intracellular magnesium and inositol 1,4,5-trisphosphate receptor: molecular mechanisms of interaction, physiology and pharmacology.

This review focuses on the action of intracellular magnesium ion on the inositol 1,4,5-trisphosphate (IP3) receptor, the almost ubiquitous membrane-bound Ca2+ channel gated by the intracellular second messenger IP3. Experimental data have shown that Mg2+ is a non-competitive inhibitor of the IP3-gated Ca2+ channel and of [3H]-IP3 binding. The relevance of the Mg2+ effect is discussed in relation to: (a) the physiological role of the IP3-induced release of Ca2+ from intracellular Ca2+ stores, i.e., Ca2+ homeostasis of activated cells, in particular cardiac myocytes; (b) the modulation exerted by changes of [Mg2+]o and [Mg2+]i on basic cardiac functions, e.g., inotropism, chronotropism and automaticity; and (c) the pathogenesis of automatic arrhythmias, caused by either early or delayed afterdepolarizations, in which IP3-induced release of Ca2+ may be involved.