Title: Chloride influx aggravates Ca2+-dependent AMPA receptor-mediated motoneuron death
Authors: Van Damme, Philip ×
Callewaert, Geert
Eggermont, Jan
Robberecht, Wim
Van Den Bosch, Ludo #
Issue Date: Jun-2003
Publisher: The Society for Neuroscience
Series Title: Journal of Neuroscience vol:23 issue:12 pages:4942-50
Abstract: AMPA receptor-mediated excitotoxicity has been implicated in the pathogenesis of stroke, neurotrauma, epilepsy, and many neurodegenerative diseases such as motoneuron disease. We studied the role of Cl- in AMPA receptor-mediated Ca2+-dependent excitotoxicity in cultured rat spinal motoneurons. Using the gramicidin perforated patch-clamp technique, the intracellular Cl- concentration could be calculated from the reversal potential of the GABA-induced current. The membrane depolarization caused by AMPA receptor stimulation resulted in Cl- influx through 5-nitro-2(3-phenylpropyl-amino) benzoic acid- and niflumic acid-sensitive Cl- channels. Cl- influx during AMPA receptor stimulation aggravated excitotoxic motoneuron death by two mechanisms: an increase of AMPA receptor conductance and an elevation of the Ca2+ driving force through a partial repolarization. The Cl- influx during AMPA receptor stimulation was enhanced by coadministration of GABA. This resulted in an increased Ca2+ influx and an enhanced cell death, suggesting that concomitant GABAergic stimulation may aggravate excitotoxic motoneuron death.
ISSN: 0270-6474
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Neurology
Physiology Section (-)
Laboratory for Neurobiology
Laboratory of Cellular Transport Systems
× corresponding author
# (joint) last author

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