The Impact of Chronic Magnesium Deficiency on Excitable Tissues-Translational Aspects

Neuromuscular excitability is a vital body function, and Mg is an essential regulatory cation for the function of excitable membranes. Loss of Mg homeostasis disturbs fluxes of other cations across cell membranes, leading to pathophysiological electrogenesis, which can eventually cause vital threat to the patient. Chronic subclinical Mg deficiency is an increasingly prevalent condition in the general population. It is associated with an elevated risk of cardiovascular, respiratory and neurological conditions and an increased mortality. Magnesium favours bronchodilation (by antagonizing Ca channels on airway smooth muscle and inhibiting the release of endogenous bronchoconstrictors). Magnesium exerts antihypertensive effects by reducing peripheral vascular resistance (increasing endothelial NO and PgI release and inhibiting Ca influx into vascular smooth muscle). Magnesium deficiency disturbs heart impulse generation and propagation by prolonging cell depolarization (due to Na/K pump and K channel dysfunction) and dysregulating cardiac gap junctions, causing arrhythmias, while prolonged diastolic Ca release (through leaky RyRs) disturbs cardiac excitation-contraction coupling, compromising diastolic relaxation and systolic contraction. In the brain, Mg regulates the function of ion channels and neurotransmitters (blocks voltage-gated Ca channel-mediated transmitter release, antagonizes NMDARs, activates GABARs, suppresses nAChR ion current and modulates gap junction channels) and blocks ACh release at neuromuscular junctions. Magnesium exerts multiple therapeutic neuroactive effects (antiepileptic, antimigraine, analgesic, neuroprotective, antidepressant, anxiolytic, etc.). This review focuses on the effects of Mg on excitable tissues in health and disease. As a natural membrane stabilizer, Mg opposes the development of many conditions of hyperexcitability. Its beneficial recompensation and supplementation help treat hyperexcitability and should therefore be considered wherever needed.