Mechanisms of glutamate‐stimulated Mg2+ influx and subsequent Mg2+ efflux in rat forebrain neurones in culture.

  title={Mechanisms of glutamate‐stimulated Mg2+ influx and subsequent Mg2+ efflux in rat forebrain neurones in culture.},
  author={Amy K. Stout and Yingying Li-Smerin and J. W. Johnson and Ian J Reynolds},
  journal={The Journal of Physiology},
1. Mag‐fura‐2 fluorescence microscopy and whole‐cell patch‐clamp recordings were used to measure glutamate‐induced changes in the intracellular free Mg2+ concentration ([Mg2+]i) and Mg2+ currents, respectively, in cultured forebrain neurones from fetal rats in the absence of extracellular Na+ (Nao+) and Ca2+ (Cao2+). 2. Increasing the extracellular Mg2+ concentration ([Mg2+]o) from 9 to 70 mM significantly enhanced the maximum [Mg2+]i induced by a 5 min 100 microM glutamate plus 1 microM… 

Glutamate‐induced calcium increase mediates magnesium release from mitochondria in rat hippocampal neurons

The results support the idea that glutamate is able to induced Mg2+ efflux from mitochondria to the cytosol and that Ca2+ accumulation in the mitochondria is required for this M g2+ release.

Modulation by permeant ions of Mg2+ inhibition of NMDA‐activated whole‐cell currents in rat cortical neurons

A powerful effect of changing permeant ion concentrations on the voltage‐dependent inhibition by external Mg2+ (Mg2- (Mgo2+) of NMDA‐activated currents is reported, consistent with a model in which Nai+ and Csi+ modulate Mgo2+ inhibition ofNMDA‐ activated currents by occupying external permeant ions binding sites.

Mitochondria accumulate Ca2+ following intense glutamate stimulation of cultured rat forebrain neurones.

The studies suggest that mitochondria become progressively more important for buffering glutamate‐induced Ca2+ loads as the stimulus intensity increases, and highlight a previously under‐appreciated role for [Na+]i in the regulation of [Ca2+] i in central neurones.

Free intracellular Mg2+ concentration and inhibition of NMDA responses in cultured rat neurons

Results of cell‐attached recording and modelling of whole‐cell data suggest that the Mg2+i‐induced stabilisation of the channel open state is four times weaker after patch excision than in intact cells.

The role of intracellular Na+ and mitochondria in buffering of kainate‐induced intracellular free Ca2+ changes in rat forebrain neurones

It is revealed that mitochondria have a central role in buffering neuronal [Ca2+]i changes mediated by non‐N‐methyl‐D‐aspartate (NMDA) glutamate receptors, and that the variation in recovery times following kainate receptor activation reflects a variable degree of mitochondrial Ca2+ loading.

NMDA Receptor‐Mediated Neurotoxicity: A Paradoxical Requirement for Extracellular Mg2+ in Na+/Ca2+‐Free Solutions in Rat Cortical Neurons In Vitro

The increase in intracellular Mg2+ concentration following NMDA receptor stimulation may be an underestimated component critical for the expression of certain forms of excitotoxic injury.

Reverse Na+/Ca2+ exchange contributes to glutamate-induced intracellular Ca2+ concentration increases in cultured rat forebrain neurons.

Reverse NCE contributes to the immediate rise in [Ca2+]i resulting from glutamate receptor activation, however, reverse NCE becomes less important as the stimulus time is increased, and Ca2+ entry by this route is not critical for the expression of excitotoxic injury.

Intracellular sodium concentration in cultured cerebellar granule cells challenged with glutamate.

The results were interpreted to indicate that the glutamate-evoked calcium influx may lead to sodium homeostasis destabilization, and the delay in the restoration of the sodium gradient may in turn prolong the neuronal exposure to toxic [Ca2+]i values, due to the decrease in the efficiency of the Na+/ Ca2+ exchanger to extrude calcium.

Kinetics of the block by intracellular Mg2+ of the NMDA‐activated channel in cultured rat neurons.

The very fast rate constants of the block by Mgi2+ explain why channel flicker was not fully resolvable during block of the NMDA‐activated single‐channel current, and an energy profile of three barriers and two binding sites for Mg2+ is proposed.

Glutamate receptor-induced 45Ca2+ accumulation in cortical cell culture correlates with subsequent neuronal degeneration

With brief exposure, high concentrations of AMPA, kainate, or K+ produced much less death or 45Ca2+ accumulation than produced by glutamate, especially if 10 microM MK-801 was included in the exposure medium to block NMDA receptor activation.

The role of divalent cations in the N‐methyl‐D‐aspartate responses of mouse central neurones in culture.

Single‐channel currents activated by N‐methyl‐D‐aspartate (NMDA) agonists were analysed in the presence of various extracellular concentrations of divalent cations in outside‐out patches from mouse neurones in primary culture to investigate the effects of Ca2+ on currents flowing through NMDA channels.

Monitoring cytosolic free magnesium in cultured chicken heart cells by use of the fluorescent indicator Furaptra.

The data suggest that [Mg2+]i is altered by calcium, most likely due to a competition for intracellular binding sites, as well as an increase in cytosolic free calcium (intracellular sodium-extracellular calcium exchange).

Magnesium gates glutamate-activated channels in mouse central neurones

The voltage dependence of the NMDA receptor-linked conductance appears to be a consequence of the voltage dependenceof the Mg2+ block and its interpretation does not require the implication of an intramembrane voltage-dependent ‘gate’.

Permeation and block of N‐methyl‐D‐aspartic acid receptor channels by divalent cations in mouse cultured central neurones.

Manganese both permeates and blocks the NMDA receptor channel, implying an apparent increase in PCa/PNa on lowering [Na+]o and may result from interaction of permeant ions within the channel.