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.
Volpe
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Centro di Studio per la Biologia e la Fisiopatologia Muscolare del CNR, Padova, Italy.
Vezú
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D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008274:Magnesium / Q000494:pharmacology / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems; D012964:Sodium / Q000378:metabolism
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D012964:Sodium; D008274:Magnesium; D002118:Calcium