Human neocortical excitability is decreased during anoxia via sodium channel modulation

Theodore Cummins, Chun Jiang, Gabriel G. Haddad

Research output: Contribution to journalArticle

69 Citations (Scopus)

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∞ (V)] curve for the voltage-dependent sodium current (INa). Inclusion of ATP in the patch pipette decreased the shift of the h∞ (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.

Original languageEnglish (US)
Pages (from-to)608-615
Number of pages8
JournalJournal of Clinical Investigation
Volume91
Issue number2
StatePublished - Feb 1993
Externally publishedYes

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Sodium Channels
Oxygen
Neurons
Pyramidal Cells
Central Nervous System
Adenosine Triphosphate
Sodium
Membranes
Hypoxia
Brain

Keywords

  • Ischemia
  • Metabolic inhibition
  • Neurons
  • Oxygen deprivation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Human neocortical excitability is decreased during anoxia via sodium channel modulation. / Cummins, Theodore; Jiang, Chun; Haddad, Gabriel G.

In: Journal of Clinical Investigation, Vol. 91, No. 2, 02.1993, p. 608-615.

Research output: Contribution to journalArticle

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