The FASEB Journal, Vol 3, 2519-2526, Copyright © 1989 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

A role for Na+-dependent Ca2+ extrusion in protection against neuronal excitotoxicity

MP Mattson, PB Guthrie and SB Kater
Sanders-Brown Center on Aging, University of Kentucky Medical Center, Lexington 40536.

The hypothesis that Na+-dependent calcium extrusion is important in protecting against neuronal excitotoxicity was tested. In cocultures of embryonic rat hippocampal neurons and mouse neuroblastoma hybrid (NCB- 20) cells, calcium ionophore A23187 (1 microM) or high levels of extracellular K+ killed hippocampal neurons selectively, leaving NCB-20 cells unscathed. Hippocampal neurons showed large, sustained rises in intracellular calcium in response to A23187 or K+, whereas NCB-20 cells showed only transient calcium responses. The ability of NCB-20 cells to reduce the calcium load and to survive exposure to A23187 or K+ were dependent on extracellular Na+, suggesting that an active Na+/Ca2+ exchange mechanism was important in protecting against cell death. Finally, removal of extracellular Na+ reduced the threshold for glutamate neurotoxicity in hippocampal neurons, demonstrating the importance of Na+/Ca2+ exchange in protecting against excitotoxicity. Taken together, these findings suggest that differences in cell calcium- regulating systems may determine whether a neuron lives or degenerates in the face of an excitatory challenge.

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