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Science 13 December 1996: Vol. 274. no. 5294, pp. 1921 - 1923 DOI: 10.1126/science.274.5294.1921
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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
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.
To whom correspondence should be addressed. E-mail:
lsatin{at}gems.vcu.edu
Read the Full Text
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