SECONDARY ACTIVATION OF A CATION CONDUCTANCE IS RESPONSIBLE FOR NMDA TOXICITY IN ACUTELY ISOLATED HIPPOCAMPAL-NEURONS

One of the key questions concerning glutamate toxicity is how a transi ent NMDA exposure can lead to a delayed death of neurons. To address t his issue, we performed whole-cell recording on acutely isolated hippo campal CA1 neurons to monitor the membrane response after NMDA exposur e. Transient NMDA exposure (100 mu M, 10 min) induced an inward curren t (postexposure current; I-pe) which was associated with a Ca2+- and N a+-permeable cation conductance. I-pe continuously increased (in the a bsence of NMDA) until death of the neuron occurred. Application of NMD A in the absence of extracellular calcium failed to trigger I-pe and n euronal death. Postexposure suppression of I-pe protected against NMDA toxicity. These results indicate that a cation current, which is indu ced by an increase in intracellular calcium concentration ([Ca2+](i)) and is itself partly carried by Ca2+, links the initial NMDA exposure to neuronal death.