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Science 13 December 1996:
Vol. 274. no. 5294, pp. 1921 - 1923
DOI: 10.1126/science.274.5294.1921

Reports

Reduction of Voltage-Dependent Mg2+ Blockade of NMDA Current in Mechanically Injured Neurons

Lei Zhang, * Beverly A. Rzigalinski, Earl F. Ellis, Leslie S. Satin dagger

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 (Mg2+) block of NMDA currents in cultured rat cortical neurons were examined. Stretch-induced injury was found to reduce the Mg2+ blockade, resulting in significantly larger ionic currents and increases in intracellular free calcium (Ca2+) concentration after NMDA stimulation of injured neurons. The Mg2+ blockade was partially restored by increased extracellular Mg2+ 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.

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Post Office Box 980524, Richmond, VA 23298-0524, USA.
*   Present address: University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.

dagger    To whom correspondence should be addressed. E-mail: lsatin{at}gems.vcu.edu


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