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Dysfunction of M-channel enhances propagation of neuronal excitability in rat hippocampus monitored by multielectrode dish and microdialysis systems.

Abstract
To explore the pathogenesis of benign familial neonatal convulsions (BFNC), we determined effects of KCNQ-related M-channels (KCNQ-channels) on hippocampal glutamate (Glu) and gamma-aminobutyric acid (GABA) releases using microdialysis, and propagation of evoked field-potentials (FP) using multielectrode (64-ch)-dish system as two-dimensional monitoring. KCNQ-channel inhibitor, Dup996, enhanced hippocampal K(+)-evoked Glu and GABA releases without affecting basal releases of them. Dup996 unaffected FP-amplitude, but enhanced FP-propagation. The GABA(A)-receptor antagonist, bicuculline, enhanced the stimulatory effects of Dup996 on FP-propagation, however, this stimulatory effects of Dup996 were abolished by the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/glutamate-receptor antagonist, DNQX. These results suggest that the occurrence of BFNC cannot be produced by KCNQ-channel dysfunction alone, but by reciprocal action between impaired KCNQ-channel and other unknown elements (possibly dysfunction of inhibitory neurotransmission system).
AuthorsG Zhu, M Okada, T Murakami, A Kamata, Y Kawata, K Wada, S Kaneko
JournalNeuroscience letters (Neurosci Lett) Vol. 294 Issue 1 Pg. 53-7 (Nov 10 2000) ISSN: 0304-3940 [Print] Ireland
PMID11044585 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Indoles
  • KCNQ Potassium Channels
  • KCNQ2 Potassium Channel
  • KCNQ3 Potassium Channel
  • Kcnq2 protein, rat
  • Kcnq3 protein, rat
  • Kcnq5 protein, rat
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Pyridines
  • Quinoxalines
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • FG 9041
  • linopirdine
  • Potassium
  • Bicuculline
Topics
  • Action Potentials (drug effects)
  • Animals
  • Bicuculline (pharmacology)
  • Electrodes
  • Epilepsy, Benign Neonatal (etiology, metabolism)
  • Excitatory Amino Acid Antagonists (pharmacology)
  • Excitatory Postsynaptic Potentials (drug effects)
  • GABA Antagonists (pharmacology)
  • Glutamic Acid (metabolism)
  • Hippocampus (cytology, drug effects, metabolism)
  • In Vitro Techniques
  • Indoles (pharmacology)
  • KCNQ Potassium Channels
  • KCNQ2 Potassium Channel
  • KCNQ3 Potassium Channel
  • Male
  • Microdialysis (methods)
  • Neurons (cytology, drug effects, metabolism)
  • Potassium (metabolism, pharmacology)
  • Potassium Channels (metabolism)
  • Potassium Channels, Voltage-Gated
  • Pyridines (pharmacology)
  • Quinoxalines (pharmacology)
  • Rats
  • Rats, Wistar
  • gamma-Aminobutyric Acid (metabolism)

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