title: Molecular basis of species-specific expression of repolarizing K+ currents in the heart.
abstract: There are important species-specific differences in K+ current profiles and arrhythmia susceptibility, but interspecies comparisons of K+ channel subunit expression are lacking. We quantified voltage-gated K+ channel (Kv) subunit mRNA and protein in rabbits, guinea pigs, and humans. Kv1.4, Kv4.2, and Kv4.3 mRNA was present in rabbits but undetectable in guinea pigs. MinK mRNA concentration in guinea pigs was almost threefold greater versus humans and 20-fold versus rabbits. MinK protein expression in guinea pigs was almost twofold that in humans and sixfold that in rabbits. KvLQT1 mRNA concentration was greatest in humans, and protein expression in humans was increased by approximately 2- and approximately 7-fold compared with values in rabbits and guinea pigs, respectively. The ether-a-go-go-related gene (ERG1) mRNA was more concentrated in humans, but ERG1 protein expression could not be compared across species because of epitope sequence differences. We conclude that important interspecies differences in cardiac K+ channel subunit expression exist and may contribute to the following: 1) lack of a transient outward current in the guinea pig (alpha-subunit transcription absent in the guinea pig heart); 2) small slow delayed rectifier current and torsades de pointes susceptibility in the rabbit (low-level minK expression); and 3) large slow component of the delayed rectifier current in the guinea pig (strong minK expression).
authors.affiliation: Department of Medicine and Research Center, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada H1T 1C8.
authors.forename: Stephen
authors.initials: S
authors.lastname: Zicha
authors.forename: Isaac
authors.initials: I
authors.lastname: Moss
authors.forename: Bruce
authors.initials: B
authors.lastname: Allen
authors.forename: Andras
authors.initials: A
authors.lastname: Varro
authors.forename: Julius
authors.initials: J
authors.lastname: Papp
authors.forename: Robert
authors.initials: R
authors.lastname: Dumaine
authors.forename: Charles
authors.initials: C
authors.lastname: Antzelevich
authors.forename: Stanley
authors.initials: S
authors.lastname: Nattel
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004594:Electrophysiology; D006168:Guinea Pigs / Q000378:metabolism*; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051672:Shal Potassium Channels; D013045:Species Specificity
chemical_list: C497018:KCND2 protein, human; D015221:Potassium Channels; D012333:RNA, Messenger; D051672:Shal Potassium Channels