Cloning, expression, and distribution of a Ca(2+)-activated K+ channel beta-subunit from human brain.
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.
Tseng-Crank
J
J
Glaxo-Wellcome Research Institute, Research Triangle Park, NC 27709, USA.
Godinot
N
N
Johansen
T E
TE
Ahring
P K
PK
Strøbaek
D
D
Mertz
R
R
Foster
C D
CD
Olesen
S P
SP
Reinhart
P H
PH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry / Q000235:genetics*; D002118:Calcium / Q000494:pharmacology*; D002417:Cattle; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D003001:Cloning, Molecular; D003337:Corpus Callosum / Q000737:chemistry; D006624:Hippocampus / Q000737:chemistry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015640:Ion Channel Gating; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014018:Tissue Distribution; D014981:Xenopus
D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; D011994:Recombinant Proteins; D002118:Calcium