Mechanisms of intracellular calcium accumulation in the CA1 region of rat hippocampus during anoxia in vitro.
There is a net movement of calcium into brain cells during anoxia and ischemia. This communication examines the mechanisms of this movement in rat hippocampal slices by analyzing changes in 45Ca2+ distribution. The CA1 pyramidal cells are the most sensitive to anoxic/ischemic damage; therefore, our measurements of Ca2+ and high-energy nucleotides are restricted to this region. The increase in intracellular Ca2+ levels during anoxia is not blocked by the Ca2+ channel blocker cobalt, nor is it blocked by N-methyl-D-aspartate receptor antagonists kynurenic acid, D-2-amino-5-phosphonovaleric acid, or ketamine. Kinetic measurements show that the rate of Ca2+ efflux across the plasmalemma during anoxia is sufficiently decreased to account for the increase in intracellular Ca2+. It thus appears that the net increase in calcium does not result from the opening of voltage-sensitive Ca2+ channels, nor from flux through the N-methyl-D-aspartate channel. Rather, it results from inhibition of the adenosine triphosphate-dependent extrusion mechanism for Ca2+. The relation of this conclusion to mechanisms of anoxic cell damage is discussed.
Lipton
P
P
Department of Physiology, University of Wisconsin, Madison.
Lobner
D
D
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D002121:Calcium Channel Blockers; D016194:Receptors, N-Methyl-D-Aspartate; D003035:Cobalt; D002118:Calcium