Cloning of a new mouse two-P domain channel subunit and a human homologue with a unique pore structure

Mouse KCNK6 is a new subunit belonging to the TWIK channel family. This 335 -amino acid polypeptide has four transmembrane segments, two pore-forming d omains, and a Ca2+-binding EF-hand motif. Expression of KCNK6 transcripts i s principally observed in eyes, lung, stomach and embryo. In the eyes, immu nohistochemistry reveals protein expression only in some of the retina neur ons. Although KCNK6 is able to dimerize as other functional two-P domain K channels when it is expressed in COS-7 cells, it remains in the endoplasmi c reticulum and is unable to generate ionic channel activity. Deletions, mu tations, and chimera constructions suggest that KCNK6 is not an intracellul ar channel but rather a subunit that needs to associate with a partner, whi ch remains to be discovered, in order to reach the plasma membrane, A close ly related human KCNK7-A subunit has been cloned. KCNK7 displays an intrigu ing GLE sequence in its filter region instead of the G(Y/F/L)G sequence, wh ich is considered to be the K+ channel signature. This subunit is alternati vely spliced and gives rise to the shorter forms KCNK7-B and -C, None of th e KCNR7 structures can generate channel activity by itself. The KCNK7 gene is situated on chromosome 11, in the q13 region, where several candidate di seases have been identified.