We want to thank Dr. Y. Kubo (Tokyo Metropolitan Institute for Neuroscience) for discussions on the manuscript, A. Kushi, K. Akiyama, and Y. Yamasaki for helpful advice on mouse breeding, and S. Nakanishi for histology techniques. We also thank M. Kumai, K. Ishii, H. Nakano, M. Yamasaki, and I. Sugamuma for help in generating and caring for the deficient mice used in this study and S. Inoue and M. Saito for their expert technical assistance. We thank Dr. M. Takase for the EEG work and helpful discussions.

  • 1
    Baker P.F. & Knight D.E. (1978) Calcium-dependent exocytosis in bovine adrenal medullary cells with leaky plasma membranes.Nature 76,620622.
  • 2
    Baraitser M. (1990) Epilepsy, inThe Genetics of Neurological Disorders, 2nd edit.( Oxford Monographs on Medical Genetics, Vol. 18), pp. 96113. Oxford University Press, New York.
  • 3
    Biervert C. & Steinlein O.K. (1999) Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions.Hum. Genet. 104,234240.
  • 4
    Biervert C., Schroeder B.C., Kubisch C., Berkovic S.F., Propping P., Jentsch T.J., Steinlein O.K. (1998) A potassium channel mutation in neonatal human epilepsy.Science 279,403406.
  • 5
    Charlier C., Singh N.A., Ryan S.G., Lewis T.B., Reus B.E., Leach R.J., Leppert M. (1998) A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family.Nat. Genet. 18,5355.
  • 6
    Gonzalez-Garcia C., Cena V., Keiser H.R., Rojas E. (1993) Catecholamine secretion induced by tetraethylammonium from cultured bovine adrenal chromaffin cells.Biochim. Biophys. Acta 1177,99105.
  • 7
    Hollingsworth M. & Gilfillan A.M. (1984) The pharmacology of lung surfactant secretion.Pharmacol. Rev. 36,6990.
  • 8
    Kanno T. (1977) The relationship between changes in electrophysiological properties of adrenal chromaffin cells and catecholamine release, inChromaffin, Enterochromaffin and Related Cells, pp. 4757. Elsevier Scientific, Amsterdam.
  • 9
    Kubisch C., Schroeder B.C., Friedrich T., Lütjohann B., El-Amraoui A., Marlin S., Petit C., Jentsch T.J. (1999) KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.Cell 96,437446.
  • 10
    Leppert M., Anderson V.E., Quattlebaum T., Stauffer D., O'Connell P., Nakamura Y., Lalouel J.M., White R. (1989) Benign familial neonatal convulsions linked to genetic markers on chromosome 20.Nature 337,647648.
  • 11
    Lerche H., Biervert C., Alekov A.K., Schleithoff L., Linder M., Klingler W., Bretschneider F., Mitrovic N., Jurkat-Rott K., Bode H., Lehmann-Horn F., Steinlein O.K. (1999) A reduced K+ current due to a novel mutation in KCNQ2 causes neonatal convulsions.Ann. Neurol. 46,305312.
  • 12
    Lewis T.B., Leach R.J., Ward K., O'Connell P., Ryan S.G. (1993) Genetic heterogeneity in benign familial neonatal convulsions : identification of a new locus on chromosome 8q.Am. J. Hum. Genet. 53,670675.
  • 13
    Mansour S.L., Thomas K.R., Capecchi M.R. (1988) Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells : a general strategy for targeting mutations to non-selectable genes.Nature 336,348352.
  • 14
    Matsumoto M., Nakagawa T., Inoue T., Nagata E., Tanaka K., Takano H., Minowa O., Kuno J., Sakakibara S., Yamada M., Yoneshima H., Miyawaki A., Fukuuchi Y., Furuichi T., Okano H., Mikoshiba K., Noda T. (1996) Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-trisphosphate receptor.Nature 379,168171.
  • 15
    Nagata E., Takase M., Fukuuchi Y., Tanaka K., Matsumoto M., Suzuki S., Dembo T., Mikoshiba K. (1998) Neurological aspects of mice heterozygous for type 1 inositol 1,4,5-trisphosphate receptor—electroencephalographic study. (Abstr.) Neurosci. Res. Suppl. 22,S337.
  • 16
    Nakamura M., Watanabe H., Kubo Y., Yokoyama M., Matsumoto T., Sasai H., Nishi Y. (1998) KQT2, a new putative potassium channel family produced by alternative splicing. Isolation, genomic structure, and alternative splicing of the putative potassium channels.Receptors Channels 5,255271.
  • 17
    Psenka T.M. & Holden K.R. (1996) Benign familial neonatal convulsions ; psychosocial adjustment to the threat of recurrent seizures.Seizure 5,243245.
  • 18
    Schroeder B.C., Kubisch C., Stein V., Jentsch T.J. (1998) Moderate loss of function of cyclic-AMP-modulated KNCQ2/KNCQ3 K+ channels causes epilepsy.Nature 396,687690.
  • 19
    Singh N.A., Charlier C., Stauffer D., DuPont B.R., Leach R.J., Melis R., Ronen G.M., Bjerre I., Quattlebaum T., Murphy J.V., McHarg M.L., Gagnon D., Rosales T.O., Peiffer A., Anderson V.E., Leppert M. (1998) A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.Nat. Genet. 18,2529.
  • 20
    Singh R., Scheffer I.E., Crossland K., Berkovic S.F. (1999) Generalized epilepsy with febrile seizures plus : a common childhood-onset genetic epilepsy syndrome.Ann. Neurol. 45,7581.
  • 21
    Slotkin T.A. & Seidler F.J. (1988) Adrenomedullary catecholamine release in the fetus and newborn : secretory mechanisms and their role in stress and survival.J. Dev. Physiol. 10,116.
  • 22
    Steinlein O., Schuster V., Fischer C., Haussler M. (1995) Benign familial neonatal convulsions : confirmation of genetic heterogeneity and further evidence for a second locus on chromosome 8q.Hum. Genet. 95,411415.
  • 23
    Tinel N., Lauritzen I., Chouabe C., Lazdunski M., Borsotto M. (1998) The KCNQ2 potassium channel : splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3.FEBS Lett. 438,171176.
  • 24
    Wang H.S., Pan Z., Shi W., Brown B.S., Wymore R.S., Cohen I.S., Dixon J.E., McKinnon D. (1998) KCNQ2 and KCNQ3 potassium channel subunits : molecular correlates of the M-channel.Science 282,18901893.
  • 25
    Wang Q., Curran M.E., Splawski I., Burn T.C., Millholland J.M., VanRaay T.J., Shen J., Timothy K.W., Vincent G.M., De Jager T., Schwartz P.J., Towbin J.A., Moss A.J., Atkinson D.L., Landes G.M., Connors T.D., Keating M.T. (1996) Positional cloning of a novel potassium channel gene : KVLQT1 mutations cause cardiac arrhythmias.Nat. Genet. 12,1723.
  • 26
    Yang W.P., Levesque P.C., Little W.A., Conder M.L., Ramakrishnan P., Neubauer M.G., Blanar M.A. (1998) Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy.J. Biol. Chem. 273,1941919423.
  • 27
    Yokoyama M., Nishi Y., Yoshii J., Okubo K., Matsubara K. (1996) Identification and cloning of neuroblastoma-specific and nerve tissue-specific genes through compiled expression profiles.DNA Res. 3,311320.