TASK-5, a novel member of the tandem pore K+ channel family

We have cloned a novel member of the tandem pore K+ channel family from hum an brain cDNA. The novel cDNA encodes a 330-residue polypeptide of predicte d molecular mass 36 kDa. We have named the channel TASK-5 owing to its sequ ence homology with TASK-1 and TASK-3. TASK-5 mRNA is expressed in pancreas, liver, kidney. lung, ovary, testis and heart. However, expression of TASK- 5 in heterologous systems failed to elicit ionic currents. Removal of a put ative endoplasmic reticulum retention sequence did not alter this finding a nd the distribution of channel proteins in HEK293 cells was similar for bot h TASK-1 and TASK-5. We tested whether TASK-5 could form heteromers with TA SK-1. We show a mutant form of TASK-1 (H98N) to have a radically reduced se nsitivity to acidification. Proton sensitivity could be rescued by injectin g equimolar amounts of wild-type and mutant TASK-1 cRNA into Xenopus oocyte s; the effect was that expected if half the channels formed are heteromers. Co-expression of TASK-5 with TASK-1 H98N does not affect the proton sensit ivity of mutant TASK-1: thus TASK-5 appears not to form heteromers with TAS K-1. Nonetheless. TASK-5 may require some other, unidentified partner subun it to form functional channels in the plasma membrane or it may form a chan nel in an intracellular organelle.