Reduction of voltage-dependent Mg<sup>2+</sup> blockade of NMDA current in mechanically injured neurons

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

Affiliations

¹Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth Unversity, Post Office Box 980524, Richmond, VA 23298-0524, USA

Abstract

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.

Links

DOI: 10.1126/science.274.5294.1921

PubMed: 8943207

WoS: A1996VY20000047

History

Received: 1996-06-05

Accepted: 1996-10-08

Cited Works (1)

Year	Entry
1995	Ellis EF, McKinney JS, Willoughby KA, Liang S, Povlishock JT. A new model for rapid stretch-induced injury of cells in culture: characterization of the model using astrocytes. J Neurotrauma. June 1995;12(3):325-339.

Cited By (20)

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2012	Patel TP, Ventre SC, Meaney DF. Dynamic changes in neural circuit topology following mild mechanical injury in vitro. Ann Biomed Eng. January 2012;40(1):23-36.
2011	Meaney DF, Smith DH. Biomechanics of concussion. Clin Sports Med. January 2011;30(1):19-31.
1998	Morrison B III, Saatman KE, Meaney DF, McIntosh TK. In vitro central nervous system models of mechanically induced trauma: a review. J Neurotrauma. November 1998;15(11):911-928.
2006	Geddes-Klein DM, Schiffman KB, Meaney DF. Mechanisms and consequences of neuronal stretch injury in vitro differ with the model of trauma. J Neurotrauma. February 2006;23(2):193-204.
2015	Kang WH. Reducing the Societal Costs of Traumatic Brain Injury: Astrocyte-Based Therapeutics and Functional Injury Tolerance of the Living Brain [PhD thesis]. Columbia University; 2015.
2017	Vogel EW III. Pathobiological Mechanisms and Treatment of Electrophysiological Dysfunction Following Primary Blast-Induced Traumatic Brain Injury [PhD thesis]. Columbia University; 2017.
2004	Prado GR. Neuronal Plasma Membrane Disruption in Traumatic Brain Injury [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; July 2004.
2010	Vernekar VN. Optimization of 3-D Neural Culture and Extracellular Electrophysiology for Studying Injury-Induced Morphological and Functional Changes [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; May 2010.
2011	Wester B. Development and Characterization of Mechanically Actuated Microtweezers for Use in a Single-Cell Neural Injury Model [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; May 2011.
1999	Morrison B III. Differential Genomic Expression After Mechanical Injury of Organotypic Brain Slice Cultures: An in Vitro Model of Traumatic Brain Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 1999.
2002	Lusardi TAG. Initiation and Propagation of Mechanically Induced Neuronal Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2002.
2005	DeRidder MN. The Role of Cell Kinematics and the N-Methyl D-Aspartate Receptor in Apoptosis and Necrosis in the in Vitro Hippocampus Following Mechanical Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2005.
2010	Miller W. Mechanisms of Astrocytic Calcium Wave Propagation and in Vitro Hippocampal Cell Death Are Determined by the Magnitude of Mechanical Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2010.
2010	Spaethling JM. Signaling Leading to Calcium-Permeable AMPA Receptors and Their Role in Neuronal Loss Following Mechanical Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2010.
2010	von Reyn CR. Calpain Mediated Proteolysis of Voltage Gated Sodium Channels and Its Role in Pathological Development After Traumatic Brain Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2010.
2011	Mesfin MN. Phosphorylation-Mediated Signaling After Mechanical Neuronal Injury: An Investigation of Striatal Enriched Tyrosine Phosphatase and Elk-1 [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2011.
2011	Singh P. An in Vitro and in Silico Investigation of the Role of NMDA Receptor Subtypes Following Mechanical Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2011.
2013	Patel T. The Impact of Mild Traumatic Brain Injury on Neuronal Networks and Neurobehavior [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2013.
2020	Gabrieli DJ. Multiscale Predictions of Mechanical Response and Computational Circuit Dynamics After Traumatic Brain Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2020.
2020	Schumm SN. Computational Investigations of Neuronal Network Responses to Traumatic Brain Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2020.