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Glutamate, NMDA, and AMPA induced changes in extracellular space volume and tortuosity in the rat spinal cord.
Vargova L, Jendelova P, Chvatal A, Sykova E.
Department of Neuroscience, 2nd Medical Faculty, and Center for Cell Therapy and Tissue Repair, Charles University, and Department of Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Glutamate release, particularly in pathologic conditions, may result
in cellular swelling. The authors studied the effects of glutamate, N-methyl-d-aspartate
(NMDA), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
on extracellular pH (pHe), extracellular potassium concentration ([K+]e),
and changes in extracellular space (ECS) diffusion parameters (volume fraction
alpha, tortuosity lambda) resulting from cellular swelling. In the isolated
spinal cord of 4-to 12-day-old rats, the application of glutamate receptor
agonists induced an increase in [K+]e, alkaline-acid shifts, a substantial
decrease in alpha, and an increase in lambda. After washout of the glutamate
receptor agonists, alpha either returned to or overshot normal values,
whereas lambda remained elevated. Pretreatment with 20 mmol/L Mg++, MK801,
or CNQX blocked the changes in diffusion parameters, [K+]e and pHe evoked
by NMDA or AMPA. However, the changes in diffusion parameters also were
blocked in Ca2+-free solution, which had no effect on the [K+]e increase
or acid shift. The authors conclude that increased glutamate release may
produce a large, sustained and [Ca2+]e-dependent decrease in alpha and
increase in lambda. Repetitive stimulation and pathologic states resulting
in glutamate release therefore may lead to changes in ECS volume and tortuosity,
affecting volume transmission and enhancing glutamate neurotoxicity and
neuronal damage.
