Reduction of voltage-dependent Mg super(2+) blockade of NMDA current in mechanically injured neurons

Activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors is implicated in the pathophysiology of traumatic brain injury. Here, the effects of mechanical injury on the voltage-dependent magnesium (Mg super(2+)) block of NMDA currents in cultured rat cortical neurons were examined. Stretch-induced injury was found to reduce the Mg super(2+) blockade, resulting in significantly larger ionic currents and increases in intracellular free calcium (Ca super(2+)) concentration after NMDA stimulation of injured neurons. The Mg super(2+) blockade was partially restored by increased extracellular Mg super(2+) concentration or by pretreatment with the protein kinase C inhibitor calphostin C. These findings could account for the secondary pathological changes associated with traumatic brain injury.