Reduction of Voltage-Dependent Mg~(2+) Blockade of NMDA Current in Mechanically Injured Neurons

摘要

Activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors is implicated in the pathbphysiology of traumatic brain injury. Here, the effects of mechanical injury on the vottage-dependent magnesium (Mg~(2+)) block of NMDA currents incultured rat cortical neurons were examined. Stretch-induced injury was found to reduce the Mg~(2+) blockade, resulting in significantly larger ionic currents and increases in intracel-lular free calcium (Ca~(2+)) concentration after NMDA stimulation ofinjured neurons. The Mg~(2+) blockade was partially restored by increased extracellular Mg~(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.