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 rTHHK-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.