KQT2, A NEW PUTATIVE POTASSIUM CHANNEL FAMILY PRODUCED BY ALTERNATIVESPLICING - ISOLATION, GENOMIC STRUCTURE, AND ALTERNATIVE SPLICING OF THE PUTATIVE POTASSIUM CHANNELS

Potassium (K+) channels are critical for a variety of cell functions, including modulation of action potentials, determination of the restin g membrane potential, and development of memory and learning. Eleven m ouse cDNA clones homologous to the new human putative K+ channel (desi gnated HNSPC, which we recently reported) were isolated from the brain cDNA libraries. All these proteins coded by the isolated cDNAs were i dentical from the N-terminal to the sixth transmembrane domain, but ex hibited differences in the sequence and length of the C-terminal cytop lasmic region. Analyses of the mouse genomic DNAs showed that these cl ones originated from a single gene located on mouse chromosome 2H3-4, which proved that these clones were generated by alternative RNA splic ing. Since all isoforms showed significant structural identity with KV LQTI (64% identity in the transmembrane domains), which is known to as sociate with IsK, they were designated mKQT2.1-mKQT2.11. Northern blot analysis indicated that the mRNAs of the mKQT2 isoforms were exclusiv ely expressed in the brain. In the mouse cerebellum region, the locali zed expression of these clones in the Purkinje cell layer and Golgi ce lls was shown by in situ hybridization analysis. These transcripts wer e also detected in the mouse embryonic developmental stage (11th, 15th and 17th day); and in particular, the mRNAs for shorter forms (mKQT2. 9, mKQT2.10 or mKQT2.11) were abundantly found on the 11th day after g estation. Although these mKQT2 isoforms had the characteristic structu re of voltage-gated K+ channels, functional expression of K+ currents were not detected in Xenopus oocytes.