title: Alternative splicing determines mRNA translation initiation and function of human K(2P)10.1 K+ channels.
abstract: Potassium-selective ion channels regulate cardiac and neuronal excitability by stabilizing the resting membrane potential and by modulating shape and frequency of action potentials. The delicate control of membrane voltage requires structural and functional diversity of K+ channel subunits expressed in a given cell. Here we reveal a previously unrecognized biological mechanism. Tissue-specific mRNA splicing regulates alternative translation initiation (ATI) of human K(2P)10.1 K+ background channels via recombination of 5 nucleotide motifs. ATI-dependent expression of full-length protein or truncated subunits initiated from two downstream start codons determines macroscopic current amplitudes and biophysical properties of hK(2P)10.1 channels. The interaction between hK(2P)10.1 mRNA splicing, translation and function increases K+ channel complexity and is expected to contribute to electrophysiological plasticity of excitable cells.
authors.affiliation: Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Staudacher
authors.forename: Ioana
authors.initials: I
authors.lastname: Baldea
authors.forename: Jana
authors.initials: J
authors.lastname: Kisselbach
authors.forename: Ingo
authors.initials: I
authors.lastname: Staudacher
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Rahm
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Schweizer
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Becker
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Dierk
authors.initials: D
authors.lastname: Thomas
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D018387:Codon, Initiator; D018076:DNA, Complementary / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs; D010442:Peptide Chain Initiation, Translational / Q000235:genetics*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics* / Q000378:metabolism*; D014176:Protein Biosynthesis; D020033:Protein Isoforms; D038641:RNA 5' Terminal Oligopyrimidine Sequence; D016415:Sequence Alignment / Q000379:methods; D014982:Xenopus laevis
chemical_list: D018387:Codon, Initiator; D018076:DNA, Complementary; C503438:KCNK10 protein, human; D024683:Potassium Channels, Tandem Pore Domain; D020033:Protein Isoforms