title: Impaired M-current and neuronal excitability.
abstract: OBJECTIVE
  Benign familial neonatal convulsions (BFNC), a hereditary epilepsy, occurs specifically in newborns and remits spontaneously after this period. Several mutations of either KCNQ2 or KCNQ3, members of the KCNQ-related K+-channel (KCNQ-channel) family, were identified as a cause of BFNC. Such mutations impair KCNQ-related M- current, an element of the inhibitory system in the central nervous system (CNS), and therefore are thought to result in neuronal hyperexcitability.
  
  
  METHODS
  To clarify the pathogenesis of BFNC, this study investigated the effects of the KCNQ channel on propagation of neuronal excitability using a 64-channel multielectrode dish (MED64) system for novel two-dimensional monitoring of evoked field potentials including fiber volley (FV) and field excitatory postsynaptic potential (fEPSP).
  
  
  RESULTS
  Dup996, a selective KCNQ-channel inhibitor, did not affect the amplitude of FV or fEPSP, but enhanced the FV and fEPSP propagation. The gamma-aminobutyric acid (GABA)A-receptor antagonist, bicuculline, enhanced their propagation, whereas alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/glutamate-receptor antagonist, DNQX, reduced both amplitude and propagation of fEPSP without affecting those of FV. Under the condition of GABAA-receptor blockade by bicuculline, Dup996 enhanced the amplitude of fEPSP and propagation of FV and fEPSP without affecting the amplitude of FV. Dup996 enhanced the stimulating effects of bicuculline on the propagation and amplitude of FV and fEPSP, but it did not affect the inhibiting effects of DNQX.
  
  
  CONCLUSIONS
  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 the other unknown.
authors.affiliation: Department of Neuropsychiatry, Hirosaki University, Hirosaki, Japan. okadamot@cc.hirosaki-u.ac.jp
authors.forename: Motohiro
authors.initials: M
authors.lastname: Okada
authors.forename: Kazumaru
authors.initials: K
authors.lastname: Wada
authors.forename: Akihisa
authors.initials: A
authors.lastname: Kamata
authors.forename: Takuya
authors.initials: T
authors.lastname: Murakami
authors.forename: Gang
authors.initials: G
authors.lastname: Zhu
authors.forename: Sunao
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000367:Age Factors; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002490:Central Nervous System / Q000503:physiopathology; D003627:Data Interpretation, Statistical; D004569:Electroencephalography; D020936:Epilepsy, Benign Neonatal / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017551:Microdialysis / Q000379:methods; D009154:Mutation; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000378:metabolism / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D007211:Indoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011725:Pyridines; D011810:Quinoxalines; C056723:FG 9041; C061017:linopirdine; D001640:Bicuculline