QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (35) Citing Articles via Google Scholar Google Scholar Articles by Chen, Q. X. Articles by Wong, R. K. S. Search for Related Content PubMed PubMed Citation Articles by Chen, Q. X. Articles by Wong, R. K. S.

 Previous Article  |  Next Article 

Volume 17, Number 11, Issue of June 1, 1997 pp. 4032-4036
Copyright ©1997 Society for Neuroscience

Secondary Activation of a Cation Conductance Is Responsible for NMDA Toxicity in Acutely Isolated Hippocampal Neurons

Received Jan. 15, 1997; revised March 6, 1997; accepted March 12, 1997.

Qiang X. Chen¹, Katherine L. Perkins¹, Dennis W. Choi², and Robert K. S. Wong¹

¹ Department of Pharmacology, State University of New York Health Science Center, Brooklyn, New York 11203, and ² Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110

One of the key questions concerning glutamate toxicity is how a transient NMDA exposure can lead to a delayed death of neurons. To address this issue, we performed whole-cell recording on acutely isolated hippocampal CA1 neurons to monitor the membrane response after NMDA exposure. Transient NMDA exposure (100 µM, 10 min) induced an inward current (postexposure current; I_pe) which was associated with a Ca²⁺- and Na⁺-permeable cation conductance. I_pe continuously increased (in the absence of NMDA) until death of the neuron occurred. Application of NMDA in the absence of extracellular calcium failed to trigger I_pe and neuronal death. Postexposure suppression of I_pe protected against NMDA toxicity. These results indicate that a cation current, which is induced by an increase in intracellular calcium concentration ([Ca²⁺]_i) and is itself partly carried by Ca²⁺, links the initial NMDA exposure to neuronal death.

Key words: NMDA; neurotoxicity; postexposure current; I_pe; excitotoxicity; calcium; hippocampus; glutamate; toxicity; cell death; neuronal death

This article has been cited by other articles:

				R. J. Thompson, M. F. Jackson, M. E. Olah, R. L. Rungta, D. J. Hines, M. A. Beazely, J. F. MacDonald, and B. A. MacVicar Activation of Pannexin-1 Hemichannels Augments Aberrant Bursting in the Hippocampus Science, December 5, 2008; 322(5907): 1555 - 1559. [Abstract] [Full Text] [PDF]

				T. A. Vander Jagt, J. A. Connor, and C. W. Shuttleworth Localized Loss of Ca2+ Homeostasis in Neuronal Dendrites Is a Downstream Consequence of Metabolic Compromise during Extended NMDA Exposures J. Neurosci., May 7, 2008; 28(19): 5029 - 5039. [Abstract] [Full Text] [PDF]

				L. S. Deshpande, D. D. Limbrick Jr., S. Sombati, and R. J. DeLorenzo Activation of a Novel Injury-Induced Calcium-Permeable Channel That Plays a Key Role in Causing Extended Neuronal Depolarization and Initiating Neuronal Death in Excitotoxic Neuronal Injury J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 443 - 452. [Abstract] [Full Text] [PDF]

				Y. Shen, K. Kishimoto, D. J. Linden, and A. Sapirstein Cytosolic phospholipase A2 alpha mediates electrophysiologic responses of hippocampal pyramidal neurons to neurotoxic NMDA treatment PNAS, April 3, 2007; 104(14): 6078 - 6083. [Abstract] [Full Text] [PDF]

				C. M. Norris, E. M. Blalock, O. Thibault, L. D. Brewer, G. V. Clodfelter, N. M. Porter, and P. W. Landfield Electrophysiological Mechanisms of Delayed Excitotoxicity: Positive Feedback Loop Between NMDA Receptor Current and Depolarization-Mediated Glutamate Release J Neurophysiol, November 1, 2006; 96(5): 2488 - 2500. [Abstract] [Full Text] [PDF]

				D. A. Lupinsky and N. S. Magoski Ca2+-dependent regulation of a non-selective cation channel from Aplysia bag cell neurones J. Physiol., September 1, 2006; 575(2): 491 - 506. [Abstract] [Full Text] [PDF]

				M A Smith, P S Herson, K Lee, R D Pinnock, and M L J Ashford Hydrogen-Peroxide-Induced Toxicity of Rat Striatal Neurones Involves Activation of a Non-Selective Cation Channel J. Physiol., March 1, 2003; 547(2): 417 - 425. [Abstract] [Full Text] [PDF]

				C. W. R. Shuttleworth and J. A. Connor Strain-Dependent Differences in Calcium Signaling Predict Excitotoxicity in Murine Hippocampal Neurons J. Neurosci., June 15, 2001; 21(12): 4225 - 4236. [Abstract] [Full Text] [PDF]

				D. D. Fraser, D. Doll, and B. A. MacVicar Serine/Threonine Protein Phosphatases and Synaptic Inhibition Regulate the Expression of Cholinergic-Dependent Plateau Potentials J Neurophysiol, March 1, 2001; 85(3): 1197 - 1205. [Abstract] [Full Text] [PDF]

				J. A. Connor and R. J. Cormier Cumulative Effects of Glutamate Microstimulation on Ca2+ Responses of CA1 Hippocampal Pyramidal Neurons in Slice J Neurophysiol, January 1, 2000; 83(1): 90 - 98. [Abstract] [Full Text] [PDF]

				R. Bianchi, S. R. Young, and R. K. S. Wong Group I mGluR Activation Causes Voltage-Dependent and -Independent Ca2+ Rises in Hippocampal Pyramidal Cells J Neurophysiol, June 1, 1999; 81(6): 2903 - 2913. [Abstract] [Full Text] [PDF]

				Q. X. Chen, K. L. Perkins, and R. K. S. Wong Zn2+ Blocks the NMDA- and Ca2+-Triggered Postexposure Current Ipe in Hippocampal Pyramidal Cells J Neurophysiol, February 1, 1998; 79(2): 1124 - 1126. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help