Cloning, expression, and distribution of a Ca(2+)-activated K+ channel beta-subunit from human brain

• Published in: Proceedings of the National Academy of Sciences - PNAS 1996-08, Vol.93 (17), p.9200-9205
• Main Authors: Tseng-Crank, J, Godinot, N, Johansen, T E, Ahring, P K, Strøbaek, D, Mertz, R, Foster, C D, Olesen, S P, Reinhart, P H
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Brain Chemistry - genetics; Calcium - pharmacology; Cattle; Chromosome Mapping; Chromosomes, Human, Pair 5 - genetics; Cloning, Molecular; Corpus Callosum - chemistry; Hippocampus - chemistry; Humans; In Situ Hybridization, Fluorescence; Ion Channel Gating; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Large-Conductance Calcium-Activated Potassium Channel beta Subunits; Large-Conductance Calcium-Activated Potassium Channels; Molecular Sequence Data; Patch-Clamp Techniques; Potassium Channels - biosynthesis; Potassium Channels - drug effects; Potassium Channels - genetics; Potassium Channels, Calcium-Activated; Recombinant Proteins - biosynthesis; RNA, Messenger - isolation & purification; Sequence Homology, Amino Acid; Species Specificity; Tissue Distribution; Xenopus
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.17.9200

We have cloned and expressed a Ca(2+)-activated K+ channel beta-subunit from human brain. The open reading frame encodes a 191-amino acid protein possessing significant homology to a previously described subunit cloned from bovine muscle. The gene for this subunit is located on chromosome 5 at band q34 (hslo-beta). There is no evidence for alternative RNA splicing of this gene product. hslo-beta mRNA is abundantly expressed in smooth muscle, but expression levels are low in most other tissues, including brain. Brain subregions in which beta-subunit mRNA expression is relatively high are the hippocampus and corpus callosum. The coexpression of hslo-beta mRNA together with hslo-alpha subunits in either Xenopus oocytes or stably transfected HEK 293 cells give rise to Ca(2+)-activated potassium currents with a much increased calcium and/or voltage sensitivity. These data indicate that the beta-subunit shows a tissue distribution different to that of the alpha-subunit, and in many tissues there may be no association of alpha-subunits with beta-subunits. These beta-subunits can play a functional role in the regulation of neuronal excitability by tuning the Ca2+ and/or the voltage dependence of alpha-subunits.