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Title: Neuronal excitation by guanidines and other uremic retention solutes
Authors: D'Hooge, Rudi ×
Van Bogaert, P.P.
Marescau, B.
Van Holder, R.
De Deyn, P.P. #
Issue Date: 2001
Publisher: Published for the International Federation for Cell Biology by Academic Press
Host Document: Cell biology international vol:25 (9) pages:939-939
Conference: International meeting on Guanidino Compounds in Biology and Medicine edition:6 location:Cinncinnati, Ohio, USA date:31 August-3 September 2001
Article number: 14
Abstract: Increased neuronal excitability may underlie some of the neurological complications in uremic patients. In an effort to identify candidate neuroexcitatory compounds, 17 different uremic retention solutes, including several guanidino compounds, were applied to mouse spinal cord neurons in primary dissociated cell cultures. Using the tight-seal whole-cell technique, a few of the candidate toxins were shown to evoke whole-cell currents in cells clamped at -6o mV. In a first survey, each of the solutes was briefly applied at 5 mM. Significant inward whole-cell currents were evoked by guanidinosuccinate, spermine, and 3-indoxyl sulfate, whereas phenol evoked an outward current. Further experiments indicated that guanidinosuccinate-evoked whole-cell currents were due to activation of NMDA-type glutamate receptors in concentrations similar to those found in uremic patients. High (mM) concentrations of spermine directly activated voltage-gated calcium channels, whereas low (µM) concentrations were found to potentiate guanidinosuccinate-evoked currents through its action on the NMDA receptor-associated polyamine binding site. Whole-cell currents evoked by 3-indoxyl sulfate or phenol seemed to be due to complex interaction with several different ion channels. We conclude that guanidinosuccinate-evoked NMDA receptor activation, possibly potentiated by the neuroexcitatory effects of other putative uremic neurotoxins, could be an important mechanism underlying the increased neuroexcitability in uremic brain
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Laboratory for Biological Psychology
× corresponding author
# (joint) last author

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