The Journal of Neurophysiology Vol. 83 No. 6 June 2000, pp. 3462-3472
Copyright ©2000 by the American Physiological Society

Differential Fall in ATP Accounts for Effects of Temperature on Hypoxic Damage in Rat Hippocampal Slices

 ¹Department of Anesthesiology and  ²Department of Physiology and Pharmacology, State University of New York, Health Science Center at Brooklyn, Brooklyn, New York 11203

Wang, J., G. Chambers, J. E. Cottrell, and I. S. Kass. Differential Fall in ATP Accounts for Effects of Temperature on Hypoxic Damage in Rat Hippocampal Slices. J. Neurophysiol. 83: 3462-3472, 2000. Intracellular recordings, ATP and cytosolic calcium measurements from CA1 pyramidal cells in rat hippocampal slices were used to examine the mechanisms by which temperature alters hypoxic damage. Hypothermia (34°C) preserved ATP (1.7 vs. 0.8 nM/mg) and improved electrophysiologic recovery of the CA1 neurons after hypoxia; 58% of the neurons subjected to 10 min of hypoxia (34°C) recovered their resting and action potentials, while none of the neurons at 37°C recovered. Increasing the glucose concentration from 4 to 6 mM during normothermic hypoxia improved ATP (1.3 vs. 0.8 nM/mg) and mimicked the effects of hypothermia; 67% of the neurons recovered their resting and action potentials. Hypothermia attenuated the membrane potential changes and the increase in intracellular Ca²⁺ (212 vs. 384 nM) induced by hypoxia. Changing the glucose concentration in the artificial cerebrospinal fluid primarily affects ATP levels during hypoxia. Decreasing the glucose concentration from 4 to 2 mM during hypothermic hypoxia worsened ATP, cytosolic Ca²⁺, and electrophysiologic recovery. Ten percent of the neurons subjected to 4 min of hypoxia at 40°C recovered their resting and action potentials; this compared with 60% of the neurons subjected to 4 min of normothermic hypoxia. None of the neurons subjected to 10 min of hypoxia at 40°C recovered their resting and action potentials. Hyperthermia (40°C) worsens the electrophysiologic changes and induced a greater increase in intracellular Ca²⁺ (538 vs. 384 nM) during hypoxia. Increasing the glucose concentration from 4 to 8 mM during 10 min of hyperthermic hypoxia improved ATP (1.4 vs. 0.6 nM/mg), Ca²⁺ (267 vs. 538 nM), and electrophysiologic recovery (90 vs. 0%). Our results indicate that the changes in electrophysiologic recovery with temperature are primarily due to changes in ATP and that the changes in depolarization and Ca²⁺ are secondary to these ATP changes. Both primary and secondary changes are important for explaining the improved electrophysiologic recovery with hypothermia.