Magnesium Ions as Modulators of Voltage-Gated and Ligand-Gated Ion Channels in Central Neurons
Year: 2025
Type: article
Abstract: Magnesium ions regulate synaptic and nonsynaptic neuronal excitability from intracellular (Mg2+i) and extracellular (Mg2+o) domains, modulating voltage- and ligand-gated ion channels. K+ inward rectifier (Kir) channel inward rectification arises from Mg2+i blocking the pore and outward K+ current, while Mg2+o targets external sites. Mg2+i causes voltage-dependent Ca2+ voltage-gated (CaV) and Na+ voltage-gated (NaV) channel block while phosphorylation modulates channel activity. Mg2+o elicits direct voltage-dependent CaV channel block, and screens surface charge, and in NaV channels reduces conduction and may cause depolarization by quantum tunneling across closed channels. Mg2+i is an allosteric large conductance Ca2+-activated K+ (BK) channel activator, binding to low-affinity sites to alter Ca2+ and voltage sensitivity but reduces small conductance Ca2+-activated K+ (SK) channels’ outward K+ current and induces inward rectification. N-Methyl-D-aspartate receptor (NMDAR) channels are inhibited by Mg2+i binding within the pore, while Mg2+o stabilizes excitability through voltage-dependent block, Mg2+o forms Mg-ATP complex modifying purinergic P2X receptor (P2XR) channel affinity and gating and directly blocks the pore. Mg2+o reduces gamma-aminobutyric acid type A receptor (GABAAR) channel Cl− current amplitude and augments susceptibility to blockers. Mg2+o and Mg2+i block nicotinic acetylcholine receptor (nAChR) channels through voltage-dependent pore binding and surface charge screening, impeding current flow and altering gating.
Institution: University of Belgrade
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W4417452398