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Reduced contribution from Na + /H + exchange to acid extrusion during anoxia in adult rat hippocampal CA1 neurons
Author(s) -
Sheldon Claire,
Church John
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02169.x
Subject(s) - extracellular , chemistry , biophysics , hippocampal formation , adenosine triphosphate , antimycin a , incubation , biochemistry , medicine , endocrinology , biology , mitochondrion
The effect of anoxia on Na + /H + exchange activity was examined in acutely isolated adult rat hippocampal CA1 neurons loaded with the H + ‐sensitive fluorophore, BCECF. Five‐minute anoxia imposed under nominally HCO 3 – /CO 2 ‐free conditions induced a fall in pH i , the magnitude of which was smaller following prolonged exposure to medium in which N ‐methyl‐ d ‐glucamine (NMDG + ) was employed as an extracellular Na + (Na + o ) substitute. Also consistent with the possibility that Na + /H + exchange becomes inhibited soon after the induction of anoxia, rates of Na + o ‐dependent pH i recovery from internal acid loads imposed during anoxia were slowed, compared to rates of Na + o ‐dependent pH i recovery observed prior to anoxia. At the time at which rates of pH i recovery were reduced during anoxia, cellular adenosine triphosphate (ATP) levels had fallen to 35% of preanoxic levels, suggesting that ATP depletion might contribute to the observed inhibition of Na + /H + exchange. In support, incubation of neurons with 2‐deoxyglucose and antimycin A under normoxic conditions induced a fall in cellular ATP levels that was also associated with reduced Na + o ‐dependent rates of pH i recovery from imposed acid loads; conversely, pre‐treatment with 10 m m creatine attenuated the effects of anoxia to reduce both ATP levels and Na + o ‐dependent rates of pH i recovery from internal acid loads. Taken together, the results are consistent with the possibility that functional Na + /H + exchange activity in adult rat CA1 neurons declines soon after the onset of anoxia, possibly as a result of anoxia‐induced falls in intracellular ATP.