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 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 microM, 10 min) induced an inward current (postexposure current; Ipe) which was associated with a Ca2+- and Na+-permeable cation conductance. Ipe 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 Ipe and neuronal death. Postexposure suppression of Ipe 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.
Chen
Q X
QX
Department of Pharmacology, State University of New York Health Science Center, Brooklyn, New York 11203, USA.
Perkins
K L
KL
Choi
D W
DW
Wong
R K
RK
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D004553:Electric Conductivity; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000502:physiology; D012964:Sodium / Q000378:metabolism
D002412:Cations; D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D012964:Sodium; D002118:Calcium