title: 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).
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Hirosaki University, 036-8562, Hirosaki, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Zhu
authors.forename: M
authors.initials: M
authors.lastname: Okada
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: A
authors.initials: A
authors.lastname: Kamata
authors.forename: Y
authors.initials: Y
authors.lastname: Kawata
authors.forename: K
authors.initials: K
authors.lastname: Wada
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004566:Electrodes; D020936:Epilepsy, Benign Neonatal / Q000209:etiology / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D051656:KCNQ Potassium Channels; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D008297:Male; D017551:Microdialysis / Q000379:methods; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D007211:Indoles; D051656:KCNQ Potassium Channels; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; C496915:Kcnq2 protein, rat; C496918:Kcnq3 protein, rat; C501028:Kcnq5 protein, rat; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines; D011810:Quinoxalines; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C056723:FG 9041; C061017:linopirdine; D011188:Potassium; D001640:Bicuculline