Sj. Tavalin et al., INHIBITION OF THE ELECTROGENIC NA PUMP UNDERLIES DELAYED DEPOLARIZATION OF CORTICAL-NEURONS AFTER MECHANICAL INJURY OR GLUTAMATE, Journal of neurophysiology, 77(2), 1997, pp. 632-638
We previously characterized the electrophysiological response of corti
cal neurons to a brief sublethal stretch-injury using an in vitro mode
l of traumatic brain injury. This model revealed that cortical neurons
undergo a stretch-induced delayed depolarization (SIDD) of their rest
ing membrane potential (RMP) which is similar to 10 mV in magnitude. S
IDD is dependent on N-methyl-D-aspartate (NIMDA) receptor activation,
neuronal firing, and extracellular calcium for its induction but not i
ts maintenance. SIDD was maximal 1 h after the insult and required inc
ubation at 37 degrees C. The present study examined the mechanism medi
ating SIDD and its relation to glutamate receptor activation. The Na p
ump inhibitor ouabain was used to assess the contribution of the Na pu
mp to tile RMP of control and stretched neurons using whole cell patch
-clamp techniques. The nitric oxide(NO) synthase inhibitor N omega-nit
ro-L-arginine and a polyethylene glycol conjugate of superoxide dismut
ase were used to assess whether NO or superoxide anion, respectively,
were involved in the induction of SIDD. Neurons were exposed to exogen
ous glutamate in the absence of cell stretch to determine whether glut
amate alone can mimic SIDD. We report that SIDD is mediated by Na pump
inhibition and is likely to result from reduced energy levels since t
he RMP of neurons dialyzed with a pipette solution containing 5 mM ATP
were identical to controls. NO, but not superoxide anion, also may co
ntribute to SIDD. A 3-min exposure to 10 mu M glutamate produced a SID
D-like depolarization also associated with Na pump inhibition. The res
ults suggest that Na pump inhibition secondary to alterations in cellu
lar energetics underlies SIDD. Na pump inhibition due to glutamate exp
osure may contribute to traumatic brain injury or neurodegenerative di
seases linked to glutamate receptor activation.