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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

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