Structure and complex transcription pattern of the mouse SK1K(Ca) channel gene, KCNN1

Small conductance calcium-gated K+ channels (SK channels) are encoded by th e three SK genes, SK1, SK2, and SK3. These channels likely contribute to sl ow synaptic afterhyperpolarizations of apamin-sensitive and apamin-insensit ive types. SK channels are also widely expressed outside the nervous system . The mouse SK1 gene comprises at least 12 exons extending across 19.8 kb o f genomic DNA. This gene encodes a complex pattern of alternatively spliced SK1 transcripts widely expressed among mouse tissues. These transcripts ex hibit at least four distinct 5'-nucleotide sequence variants encoding at le ast two N-terminal amino acid sequences. Optional inclusion of exons 7 and 9, together with two alternate splice donor sites in exon 8, yields transcr ipts encoding eight variant C-terminal amino acid sequences for SK1. These include an altered putative S6 transmembrane span, modification of the C-te rminal cytoplasmic domain binding site for calmodulin, and generation of tw o alternate predicted binding sites for PDZ domain-containing proteins. 20 of the 32 predicted mouse SK1 transcripts are expressed in brain at levels sufficient to allow consistent detection. and encode 16 SK1 polypeptide var iants. Only four of these 16 polypeptides preserve the ability to bind calm odulin in a Ca2+-independent manner. Mouse SK1 also exhibits novel, strain- specific, length polymorphism of a polyglutamate repeat in the N-terminal c ytoplasmic domain. The evolutionary conservation of this complex transcript ion pattern suggests a possible role in the tuning of SK1 channel function. (C) 2001 Elsevier Science B.V. All rights reserved.