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

Neuromuscular excitability is a vital body function, and Mg²⁺ is an essential regulatory cation for the function of excitable membranes. Loss of Mg²⁺ homeostasis disturbs fluxes of other cations across cell membranes, leading to pathophysiological electrogenesis, which can eventually cause vital threat to the patient. Chronic subclinical Mg²⁺ 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 Ca²⁺ 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 PgI₂ release and inhibiting Ca²⁺ influx into vascular smooth muscle). Magnesium deficiency disturbs heart impulse generation and propagation by prolonging cell depolarization (due to Na⁺/K⁺ pump and K_ir channel dysfunction) and dysregulating cardiac gap junctions, causing arrhythmias, while prolonged diastolic Ca²⁺ release (through leaky RyRs) disturbs cardiac excitation-contraction coupling, compromising diastolic relaxation and systolic contraction. In the brain, Mg²⁺ regulates the function of ion channels and neurotransmitters (blocks voltage-gated Ca²⁺ channel-mediated transmitter release, antagonizes NMDARs, activates GABA_ARs, 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 Mg²⁺ on excitable tissues in health and disease. As a natural membrane stabilizer, Mg²⁺ opposes the development of many conditions of hyperexcitability. Its beneficial recompensation and supplementation help treat hyperexcitability and should therefore be considered wherever needed.