title: Slow ATP loss and the defense of ion homeostasis in the anoxic frog brain.
abstract: For most vertebrates, cutting off the oxygen supply to the brain results in a rapid (within minutes) loss of ATP, the failure of ATP-dependent ion-transport process, subsequent anoxic depolarization of neuronal membrane potential and consequential neuronal death. The few species that survive brain anoxia for days or months, such as the freshwater turtle Trachemys scripta, avoid anoxic depolarization and maintain brain ATP levels through a coordinated downregulation of brain energy demand processes. The frog Rana pipiens represents an intermediate in anoxia-tolerance, being able to survive brain anoxia for hours. However, the anoxic frog brain does not defend its energy stores. Instead, anoxia-tolerance appears to be related to a retarded rate of ATP depletion. To investigate the relationship between this slow ATP depletion and the loss of ionic homeostasis, cerebral extracellular K(+) concentrations were monitored and ATP levels measured during anoxia, during the initial phase of anoxic depolarization and during complete anoxic depolarization. Extracellular K(+) levels were maintained at normoxic levels for at least 3 h of anoxia, while ATP content decreased by 35 %. When ATP levels reached 0.33+/-0.06 mmol l(-1) (mean +/- S.E.M., N=5), extracellular K(+) levels slowly started to increase. This value is thought to represent a critical ATP concentration for the maintenance of ion homeostasis. When extracellular [K(+)] reached an inflection value of 4.77+/-0.84 mmol l(-1) (mean +/- S.E.M., N=5), approximately 1 h later, the brain quickly depolarized. Part of the reduction in ATP demand was attributable to an approximately 50 % decrease in the rate of K(+) efflux from the anoxic frog brain, which would also contribute to the retarded rate of increase in extracellular [K(+)] during the initial phase of anoxic depolarization. However, unlike the anoxia-tolerant turtle brain, adenosine did not appear to be involved in the downregulation of K(+) leakage in the frog brain. The increased anoxia-tolerance of the frog brain is thought to be a matter more of slow death than of enhanced protective mechanisms.
authors.affiliation: Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Knickerbocker
authors.forename: P L
authors.initials: PL
authors.lastname: Lutz
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004734:Energy Metabolism; D005110:Extracellular Space / Q000378:metabolism; D006706:Homeostasis; D002534:Hypoxia, Brain; D007477:Ions / Q000378:metabolism*; D010100:Oxygen / Q000008:administration & dosage; D011188:Potassium / Q000378:metabolism; D011894:Rana pipiens / Q000378:metabolism*
chemical_list: D007477:Ions; D000255:Adenosine Triphosphate; D011188:Potassium; D010100:Oxygen