Reduction of voltage-dependent Mg2+ blockade of NMDA current in mechanically injured neurons

• Published in: Science (American Association for the Advancement of Science) Vol. 274; no. 5294; pp. 1921 - 1923
• Main Authors: ZHANG, L, RZIGALINSKI, B. A, ELLIS, E. F, SATIN, L. S
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 13.12.1996
• Subjects: Animals; Biological and medical sciences; Brain Injuries - metabolism; Calcium - metabolism; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - metabolism; Dizocilpine Maleate - pharmacology; Enzyme Inhibitors - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Injuries of the nervous system and the skull. Diseases due to physical agents; Magnesium - pharmacology; Medical sciences; Membrane Potentials; N-Methylaspartate - pharmacology; Naphthalenes - pharmacology; Neurons - cytology; Neurons - metabolism; Patch-Clamp Techniques; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Rats; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - metabolism; Traumas. Diseases due to physical agents; Cell culture; Nervous system diseases; Calcium; Rat; Rodentia; Central nervous system; Glutamate receptor; Ionic current; Trauma; Vertebrata; Experimental disease; Mammalia; Magnesium; NMDA receptor; Brain (vertebrata)
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.274.5294.1921

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.