Hyperthermia depletes adenosine triphosphate and decreases glutamate uptake in rat hippocampal slices.
The central nervous system is especially vulnerable to hyperthermia-induced dysfunction, yet the mechanism for this susceptibility is poorly understood. High levels of adenosine triphosphate are necessary to maintain normal re-uptake of glutamate and aspartate, the major excitatory amino acids, by excitatory amino acid co-transporters. We hypothesized that excitotoxic neurotransmitters accumulate extracellularly when hyperthermia depletes adenosine triphosphate, leading to decreased uptake or release of excitatory amino acids by these co-transporters. Incubation of hippocampal slices at 42 degrees C, a temperature that results in coma in vivo, reduced adenosine triphosphate to 70% of control values and decreased uptake of the transportable excitatory amino acid analogue, D,L threo-beta-hydroxyaspartate, to 50% of control values. The degree of adenosine triphosphate depletion induced by hyperthermia was highly correlated with decreases in excitatory amino acid uptake. Severe adenosine triphosphate depletion (< or = 20% of control) induced by hyperthermia in combination with metabolic insults was highly correlated with the release of endogenous glutamate and aspartate. Preloading slices with excitatory amino acid analogues potentiated hyperthermia-induced alterations of excitatory amino acid transport, strongly suggesting that the hyperthermia-induced changes were largely due to altered excitatory amino acid co-transporter activity. Immunocytochemical studies suggested glutamate-like immunoreactivity was lost from axonal terminals during hyperthermia in a similar manner to losses induced by metabolic toxins. Hyperthermia due to infectious diseases or heat stroke my induce disorientation and coma. These dysfunctions may be due, in part, to altered excitatory amino acid transport induced by adenosine triphosphate depletion.
Madl
J E
JE
Department of Anatomy and Neurobiology, Colorado State University, Fort Collins 80523, USA.
Allen
D L
DL
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D018698:Glutamic Acid; D000255:Adenosine Triphosphate