Inhibition of the electrogenic Na pump underlies delayed depolarization of cortical neurons after mechanical injury or glutamate

Steven Tavalin, Earl F. Ellis, Leslie S. Satin

Research output: Contribution to journalArticle

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Abstract

We previously characterized the electrophysiological response of cortical neurons to a brief sublethal stretch-injury using an in vitro model of traumatic brain injury. This model revealed that cortical neurons undergo a stretch-induced delayed depolarization (SIDD) of their resting membrane potential (RMP) which is ~10 mV in magnitude. SIDD is dependent on N- methyl-D-aspartate (NMDA) receptor activation, neuronal firing, and extracellular calcium for its induction but not its maintenance. SIDD was maximal 1 h after the insult and required incubation at 37°C. The present study examined the mechanism mediating SIDD and its relation to glutamate receptor activation. The Na pump inhibitor ouabain was used to assess the contribution of the Na pump to the RMP of control and stretched neurons using whole cell patch-clamp techniques. The nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine and a polyethylene glycol conjugate of superoxide dismutase were used to assess whether NO or super oxide anton, respectively, were involved in the induction of SIDD. Neurons were exposed to exogenous glutamate in the absence of cell stretch to determine whether glutamate alone can mimic SIDD. We report that SIDD is mediated by Na pump inhibition and is likely to result from reduced energy levels since the RMP of neurons dialyzed with a pipette solution containing 5 mM ATP were identical to controls. NO, but not superoxide anion, also may contribute to SIDD. A 3-min exposure to 10 μM glutamate produced a SIDD-like depolarization also associated with Na pump inhibition. The results suggest that Na pump inhibition secondary to alterations in cellular energetics underlies SIDD. Na pump inhibition due to glutamate exposure may contribute to traumatic brain injury or neurodegenerative diseases linked to glutamate receptor activation.

Original languageEnglish (US)
Pages (from-to)632-638
Number of pages7
JournalJournal of neurophysiology
Volume77
Issue number2
DOIs
StatePublished - Jan 1 1997

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Glutamic Acid
Neurons
Membrane Potentials
Wounds and Injuries
Glutamate Receptors
Nitric Oxide
Brain Diseases
Patch-Clamp Techniques
Ouabain
N-Methyl-D-Aspartate Receptors
Nitric Oxide Synthase
Superoxides
Neurodegenerative Diseases
Oxides
Arginine
Adenosine Triphosphate
Maintenance
Calcium
Traumatic Brain Injury

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

Cite this

Inhibition of the electrogenic Na pump underlies delayed depolarization of cortical neurons after mechanical injury or glutamate. / Tavalin, Steven; Ellis, Earl F.; Satin, Leslie S.

In: Journal of neurophysiology, Vol. 77, No. 2, 01.01.1997, p. 632-638.

Research output: Contribution to journalArticle

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