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. 1993 Feb;91(2):608–615. doi: 10.1172/JCI116241

Human neocortical excitability is decreased during anoxia via sodium channel modulation.

T R Cummins 1, C Jiang 1, G G Haddad 1
PMCID: PMC287992  PMID: 8381823

Abstract

When the central nervous system in humans is deprived of oxygen, the effects are potentially disastrous. Electroencephalographic activity is lost and higher brain function ceases rapidly. Despite the importance of these effects, the mechanisms underlying the loss of cortical activity are poorly understood. Using intracellular recordings of human neocortical neurons in tissue slices, we show that, whereas anoxia produces a relatively small depolarization and modest alterations in passive properties, it causes a major decrease in excitability. Whole-cell voltage-clamp studies of acutely isolated human neocortical pyramidal neurons demonstrate that anoxia and metabolic inhibition produce a large negative shift in the steady-state inactivation [h infinity (V)] curve for the voltage-dependent sodium current (INa). Inclusion of ATP in the patch pipette decreased the shift of the h infinity (V) curve by two-thirds. Because increased inactivation of INa decreases cellular metabolic demand, we postulate that this promotes neuronal survival during periods of oxygen deprivation. These data show a novel mechanism by which anoxia links metabolism to membrane ionic conductances in human cortical neurons.

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Selected References

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