Effect of changing extracellular levels of magnesium on spontaneous activity and glutamate release in the mouse neocortical slice

Abstract

1 The mouse neocortical slice preparation, maintained in a two compartment, grease gap bath, exhibits spontaneous depolarizing activity (with or without rhythmic after potentials) after perfusion with magnesium-free artificial cerebrospinal fluid. 2 If the magnesium concentration is decrementally lowered over an extended time period, then incrementally raised following a similar time course, the spontaneous depolarizing shift activity shows a hysteresis (with regard to both frequency and amplitude), the depolarizing shifts being more resistant to magnesium during the the incremental period. 3 The amino acid content of the perfusing fluid was analysed by high performance liquid chromatography (h.p.l.c.). Although a basal efflux of 6 amino acids was quantifiable, only glutamate levels increased following superfusion of the preparation with magnesium-free, artificial cerebrospinal fluid. 4 Glutamate release increased to 266% of the resting release in the presence of magnesium within the first 12min of the change into magnesium-free artificial cerebrospinal fluid. This increase in release preceded the onset of spontaneous depolarising activity. The release of glutamate remained elevated at 182% of control up to 60min after perfusion with magnesium-free buffer, when depolarizing activity was well established. 5 A model is presented and discussed for the genesis and maintenance of the spontaneous depolarizing shifts. It is suggested that the maintenance of this spontaneous activity reflects a long term enhancement of neocortical neurone excitability which may be related to long term potentiation in the hippocampus.

Magnesium in Man: Implications for Health and Disease

“…Release of glutamate can be inhibited by high extracellular Mg 2ϩ concentrations (257,318,486). Although the exact mechanism by which Mg 2ϩ reduces glutamate release is still unknown, it could be related to the inhibition of voltage-gated Ca 2ϩ channels, as glutamate release is triggered by an influx of Ca 2ϩ after an action potential (364).…”

Dose Optimization of Intravenous Magnesium Sulfate After Acute Stroke

“…[1][2][3][4][5] Unlike the great majority of other neuroprotective agents, there is extensive clinical experience with magnesium, largely in preeclampsia/eclampsia and MI, which confirm its safety and tolerability. There are a number of possible mechanisms by which magnesium may act, including increased regional cerebral blood flow to ischemic brain areas, 6 nonspecific antagonism of all subtypes of voltage-sensitive calcium channel, 7 noncompetitive blockade of the NMDA subclass of glutamate receptor, 8 -14 glutamate release inhibition, [15][16][17] enhanced recovery of cellular energy metabolism after ischemia, 18,19 and enhanced mitochondrial calcium buffering. 20 Previous small clinical trials of MgSO 4 in acute stroke have been undertaken 21,22 without evidence of undesirable neurological or cardiovascular effects.…”

Serum Magnesium Levels and Outcomes in Patients With Acute Spontaneous Intracerebral Hemorrhage

“…This could imply that, in addition to influencing hemostasis, Mg might have possible neuroprotective effects for patients with ICH 24. Preclinical data suggest that Mg exhibits multiple complementary neuroprotective mechanisms, including inhibition of glutamate release,25 restoration of blood‐brain barrier integrity, decrease in brain edema,26 and noncompetitive antagonism of N‐methyl‐ d ‐aspartate receptor activation via blockage of voltage‐dependent calcium channels 24, 27. Moreover, the antihypertensive effect of Mg could be protective in patients with ICH 24…”