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

Qiang X. Chen, Katherine L. Perkins, Dennis W. Choi, Robert K. S. Wong
1997 Journal of Neuroscience  
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 M, 10 min) induced an inward current (postexposure current; I pe ) which was associated with a Ca 2ϩand Na ϩ -permeable cation conductance. I pe continuously increased (in the absence of
more » ... (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 ([Ca 2ϩ ] i ) and is itself partly carried by Ca 2ϩ , links the initial NMDA exposure to neuronal death.
doi:10.1523/jneurosci.17-11-04032.1997 pmid:9151719 fatcat:w2eolscxxzfahf6aolvh4476ti