Cloning, localisation and functional expression of a novel human, cerebellum specific, two pore domain potassium channel.
We have isolated, by degenerate PCR, a complementary DNA encoding a novel two pore domain potassium channel. This is the 7th functional member of the human tandem pore domain potassium channel family to be reported. It has an open reading frame of 1.125 kb and encodes a 374 amino acid protein which shows 62% identity to the human TASK-1 gene: identity to other human members of the family is 31-35% at the amino acid level. We believe this gene to be human TASK-3, the ortholog of the recently reported rat TASK-3 gene: amino acid identity between the two is 74%. 'Taqman' mRNA analysis demonstrated a very specific tissue distribution pattern, showing human TASK-3 mRNA to be localised largely in the cerebellum, in contrast rat TASK-3 was reported to be widely distributed. We have shown by radiation hybrid mapping that human TASK-3 can be assigned to chromosome 8q24.3. Human TASK-3 was demonstrated to endow Xenopus oocytes with a negative resting membrane potential through the presence of a large K(+) selective conductance. TASK-3 is inhibited by extracellular acidosis with a mid-point of inhibition around pH 6. 5, supporting the predictions from the sequence data that this is a third human TASK (TWIK-related acid sensitive K(+) channel) gene.
Chapman
C G
CG
Biotechnology and Genetics, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Essex CM19 5AW, Harlow, UK. conrad_g_chapman@sbphrd.com
Meadows
H J
HJ
Godden
R J
RJ
Campbell
D A
DA
Duckworth
M
M
Kelsell
R E
RE
Murdock
P R
PR
Randall
A D
AD
Rennie
G I
GI
Gloger
I S
IS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002531:Cerebellum / Q000378:metabolism*; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005071:Evoked Potentials / Q000502:physiology*; D014644:Genetic Variation; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009865:Oocytes / Q000502:physiology; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; C498655:KCNK9 protein, human; C407082:Kcnk9 protein, rat; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D011994:Recombinant Proteins; C420132:potassium channel subfamily K member 3