Mg2Block

Mg2Block is a term used to describe the voltage-dependent blockade of certain ion channels by extracellular magnesium ions (Mg2+), most prominently observed in NMDA-type glutamate receptors. At resting membrane potential, Mg2+ occupies a site within the NMDA receptor pore, preventing permeation of Na+, K+, and Ca2+. Depolarization reduces the affinity of Mg2+ for this site, relieving the block and allowing current flow through the channel. The blocking effect is thus strongly influenced by membrane potential and extracellular Mg2+ concentration.

Mechanistically, the NMDA receptor pore is formed by subunits GluN1 and GluN2, with a magnesium-binding site located within the ion-conducting pathway near the selectivity filter. The block is voltage-dependent and characterized by a slow unblock at depolarized potentials relative to the resting state. Biochemical and electrophysiological studies have been used to develop kinetic models that describe blocked and unblocked channel states and how subunit composition modulates Mg2+ affinity.

Physiological and clinical relevance lies in the role of Mg2Block in synaptic integration and plasticity. By requiring coincident depolarization for Ca2+ influx, Mg2Block contributes to Hebbian mechanisms underlying learning and memory. It also helps prevent excessive excitation at resting potentials, reducing excitotoxic risk under normal conditions. Pharmacological agents such as memantine and ketamine preferentially access channels in a voltage- and state-dependent manner, leveraging NMDA receptor blockade that complements natural Mg2+ block. Disruptions in Mg2Block dynamics are associated with various neurological and psychiatric conditions, highlighting its significance in neuronal signaling.