Contributions of Na+ flux and the anoxic depolarization to adenosine 5'-triphosphate levels in hypoxic/hypoglycemic rat hippocampal slices.
A 10 min exposure of rat hippocampal slices to hypoxic/hypoglycemic medium decreased tissue adenosine 5'-triphosphate (ATP) levels. Hypoxia/hypoglycemia also caused an anoxic depolarization and essentially no recovery of the synaptically evoked population spike from CA1 region recorded 30 min after re-introduction of normoxic/normoglycemic medium. Removal of Ca2+ or the addition of either the non-competitive N-methyl-D-aspartate antagonist dizocilpine maleate, the inorganic Ca2+ channel antagonist Co2+; or the Na+ channel blocker tetrodotoxin to hypoxic/hypoglycemic medium improved recovery of the evoked population spike upon re-oxygenation. Dizocilpine maleate, Co2+, and tetrodotoxin spared ATP during exposure to hypoxia/hypoglycemia. In contrast, Ca(2+)-free medium facilitated recovery of the population spike but did not preserve ATP during hypoxia/hypoglycemia. Dizocilpine maleate, Co2+ or dantrolene, when added to Ca(2+)-free medium, did not preserve ATP. Tetrodotoxin, when added to Ca(2+)-free medium, was effective in sparing ATP in hypoxic/hypoglycemic medium. To determine the effect of anoxic depolarization on ATP levels, hippocampal slices were collected just before and after the depolarization. There appeared to be an abrupt drop in ATP associated with the anoxic depolarization. We conclude that Na+ influx plays a relatively larger role in ATP consumption during hypoxia/hypoglycemia than Ca2+ influx. In addition, the anoxic depolarization imposes a large and rapid drop in ATP levels.
Fowler
J C
JC
Department of Physiology, School of Medicine, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
Li
Y
Y
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004594:Electrophysiology; D006624:Hippocampus / Q000503:physiopathology*; D007003:Hypoglycemia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D013779:Tetrodotoxin; D000255:Adenosine Triphosphate; D012964:Sodium