The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3.
Benign familial neonatal convulsions, an autosomal dominant epilepsy of newborns, are linked to mutations affecting two six-transmembrane potassium channels, KCNQ2 and KCNQ3. We isolated four splice variants of KCNQ2 in human brain. Two forms generate, after transient expression in COS cells, a potassium-selective current similar to the KCNQ1 current. L-735,821, a benzodiazepine molecule which inhibits the KCNQ1 channel activity (EC50 = 0.08 microM), also blocks KCNQ2 currents (EC50 = 1.5 microM). Using in situ hybridization, KCNQ2 and KCNQ3 have been localized within the central nervous system, in which they are expressed in the same areas, mainly in the hippocampus, the neocortex and the cerebellar cortex. During brain development, KCNQ3 is expressed later than KCNQ2.
Tinel
N
N
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, Valbonne, France.
Lauritzen
I
I
Chouabe
C
C
Lazdunski
M
M
Borsotto
M
M
D000375:Aging / Q000378:metabolism*; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D019556:COS Cells; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D014644:Genetic Variation; D006801:Humans; D017403:In Situ Hybridization; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D015221:Potassium Channels / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human; C496917:Kcnq3 protein, mouse; C115921:L 735821; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D011994:Recombinant Proteins; D001569:Benzodiazepines