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 t wo 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 member s of the family is 31-35% at the amino acid level. We believe this gene to be human TASK-3, the orthologue of the recently reported rat TASK-3 gene: a mino acid identity between the two is 74%. 'Taqman' mRNA analysis demonstra ted a very specific tissue distribution pattern, showing human TASK-3 mRNA to be localised largely in the cerebellum, in contrast rat TASK-3 was repor ted to be widely distributed. We have shown by radiation hybrid mapping tha t human TASK-3 can be assigned to chromosome 8q24.3. Human TASK-3 was demon strated to endow Xenopus oocytes with a negative resting membrane potential through the presence of a large K+ selective conductance. TASK-3 is inhibi ted 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 hum an TASK (TWIK-related acid sensitive K+ channel) gene. (C) 2000 Elsevier Sc ience B.V. All rights reserved.