Comparative responses of brain stem and hippocampal neurons to O2 deprivation: in vitro intracellular studies

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Abstract
Most mammalian neurons are known to be sensitive to oxygen availability, but the nature of the sensitivity is not well understood. Previous results have suggested that brain stem neurons may respond differently than cortical neurons during oxygen deprivation. We pursued this hypothesis by examining the time course of change in membrane potential (Vm) and input resistance (Rn) during periods of reduced oxygen availability in a tissue slice preparation. Since extracellular potassium is an important factor determining resting membrane potential, extracellular K+ activity, (K+o), was also measured. Adult rat neurons from three regions were recorded: hippocampal CA1 region, hypoglossal nucleus (XII), and dorsal vagal motor nucleus (DMNX). At the end of a 5-min hypoxic exposure, all neurons depolarized and this depolarization was greatest in XII (28.8 +/- 3.2 mV) compared with DMNX (17.8 +/- 3.7 mV) and CA1 (6.7 +/- 4.4 mV). K+o increased in all regions and was larger in DMNX (7.1 +/- 2.6 mM) and XII (5.3 +/- 2.1 mM) compared with CA1 (2.2 +/- 1.4 mM). During more severe oxygen deprivation (anoxia), neurons also depolarized at different rates with XII greater than DMNX greater than CA1. K+o increased markedly (28–36 mM) by 5 min into anoxia, and no statistical difference was observed between regions. From these results we conclude that 1) all cells tested were depolarized after 5 min of hypoxia; however, regional variability exists in the sensitivity to hypoxia; brain stem neurons depolarize faster than cortical neurons; 2) during anoxia, all brain stem and cortical neurons show a major depolarization, and 3) these differences in membrane potential cannot be solely attributed to changes in extracellular K+.

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