THIK-1 and THIK-2, a novel subfamily of tandem pore domain K+ channels.
Two cDNAs encoding novel K(+) channels, THIK-1 and THIK-2 (tandem pore domain halothane inhibited K(+) channel), were isolated from rat brain. The proteins of 405 and 430 amino acids were 58% identical to each other. Homology analysis showed that the novel channels form a separate subfamily among tandem pore domain K(+) channels. The genes of the human orthologs were identified as human genomic data base entries. They possess one intron each and were assigned to chromosomal region 14q24.1-14q24.3 (human (h) THIK-1) and 2p22-2p21 (hTHIK-2). In rat (r), THIK-1 (rTHIK-1) is expressed ubiquitously; rTHIK-2 expression was found in several tissues including brain and kidney. In situ hybridization of brain slices showed that rTHIK-2 is strongly expressed in most brain regions, whereas rTHIK-1 expression is more restricted. Heterologous expression of rTHIK-1 in Xenopus oocytes revealed a K(+) channel displaying weak inward rectification in symmetrical K(+) solution. The current was enhanced by arachidonic acid and inhibited by halothane. rTHIK-2 did not functionally express. Confocal microscopy of oocytes injected with green fluorescent protein-tagged rTHIK-1 or rTHIK-2 showed that both channel subunits are targeted to the outer membrane. However, coinjection of rTHIK-2 did not affect the currents induced by rTHIK-1, indicating that the two channel subunits do not form heteromers.
Rajan
S
S
Institut für Normale und Pathologische Physiologie, Göttingen, Germany.
Wischmeyer
E
E
Karschin
C
C
Preisig-Müller
R
R
Grzeschik
K H
KH
Daut
J
J
Karschin
A
A
Derst
C
C
D000595:Amino Acid Sequence; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D000838:Anions; D016718:Arachidonic Acid / Q000494:pharmacology; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004594:Electrophysiology; D005753:Gastric Mucosa / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006221:Halothane / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017403:In Situ Hybridization; D007438:Introns; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010802:Phylogeny; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D024683:Potassium Channels, Tandem Pore Domain; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014981:Xenopus / Q000378:metabolism
D018685:Anesthetics, Inhalation; D000838:Anions; D018076:DNA, Complementary; C586367:KCNK12 protein, human; C486603:KCNK13 protein, human; C430726:Kcnk12 protein, rat; C430725:Kcnk13 protein, rat; D008164:Luminescent Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D016718:Arachidonic Acid; D011188:Potassium; D006221:Halothane