Reduced contribution from Na+/H+ exchange to acid extrusion during anoxia in adult rat hippocampal CA1 neurons.

Abstract

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 HCO3-/CO2-free conditions induced a fall in pHi, 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 pHi recovery from internal acid loads imposed during anoxia were slowed, compared to rates of Na(+)(o)-dependent pHi recovery observed prior to anoxia. At the time at which rates of pHi 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 pHi recovery from imposed acid loads; conversely, pre-treatment with 10 mm creatine attenuated the effects of anoxia to reduce both ATP levels and Na(+)(o)-dependent rates of pHi 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.

• Authors: Claire Sheldon, John Church
• Journal: Journal of neurochemistry (J Neurochem) Vol. 88 Issue 3 Pg. 594-603 (Feb 2004) ISSN: 0022-3042 [Print] England
• PMID: 14720209 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Sodium-Hydrogen Exchangers
• Adenosine Triphosphate
• Deoxyglucose

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Cell Hypoxia (drug effects, physiology)
• Cells, Cultured
• Deoxyglucose (pharmacology)
• Down-Regulation (physiology)
• Hippocampus (drug effects, metabolism)
• Hydrogen-Ion Concentration (drug effects)
• In Vitro Techniques
• Neurons (drug effects, metabolism)
• Rats
• Rats, Wistar
• Sodium-Hydrogen Exchangers (antagonists & inhibitors, metabolism)