Inhibition of the electrogenic Na pump underlies delayed depolarization of
cortical neurons following mechanical injury or glutamate.
Tavalin, Steven J., Earl F. Ellis and Leslie S. Satin.
Department of Pharmacology and Toxicology and Department of Physiology,
Medical College of Virginia, Richmond, VA 23298-0524.
APStracts 3:0228N, 1996.
We previously characterized the electrophysiological response of cortical
neurons to a brief sublethal stretch-injury (Tavalin et al. 1995) using an in
vitro model of traumatic brain injury (Ellis et al. 1995). This model revealed
that cortical neurons undergo a stretch-induced delayed depolarization (or
SIDD) of their resting membrane potential (RMP) which is 10 mV in magnitude.
SIDD is dependent on NMDA receptor activation, neuronal firing, and
extracellular calcium for its induction but not its maintenance. SIDD was
maximal 1 hr after the insult and required incubation at 37 [acute]iC. 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 Nw-nitro-L-arginine (L-NOARG) and a polyethylene glycol
conjugate of superoxide dismutase (PEG-SOD) were used to assess whether nitric
oxide or superoxide anion 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, may also
contribute to SIDD. A 3 min exposure to 10 ÁM 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
Received 11 July 1996; accepted in final form 23 September 1996.
APS Manuscript Number J545-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996