Reduction of voltage-dependent Mg2+ 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 (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.
Zhang
L
L
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Post Office Box 980524, Richmond, VA 23298-0524, USA. lsatin@gems.vcu.edu
Rzigalinski
B A
BA
Ellis
E F
EF
Satin
L S
LS
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology*; D008564:Membrane Potentials; D016202:N-Methylaspartate / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D009281:Naphthalenes; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D011493:Protein Kinase C; C058819:calphostin C; D008274:Magnesium; D002118:Calcium