title: Inward rectifier potassium current (I K1) and Kir2 composition of the zebrafish (Danio rerio) heart.
abstract: Electrophysiological properties and molecular background of the zebrafish (Danio rerio) cardiac inward rectifier current (IK1) were examined. Ventricular myocytes of zebrafish have a robust (-6.7 ± 1.2 pA pF(-1) at -120 mV) strongly rectifying and Ba(2+)-sensitive (IC50 = 3.8 μM) IK1. Transcripts of six Kir2 channels (drKir2.1a, drKir2.1b, drKir2.2a, drKir2.2b, drKir2.3, and drKir2.4) were expressed in the zebrafish heart. drKir2.4 and drKir2.2a were the dominant isoforms in both the ventricle (92.9 ± 1.5 and 6.3 ± 1.5%) and the atrium (28.9 ± 2.9 and 64.7 ± 3.0%). The remaining four channels comprised together less than 1 and 7 % of the total transcripts in ventricle and atrium, respectively. The four main gene products (drKir2.1a, drKir2.2a, drKir2.2b, drKir2.4) were cloned, sequenced, and expressed in HEK cells for electrophysiological characterization. drKir2.1a was the most weakly rectifying (passed more outward current) and drKir2.2b the most strongly rectifying (passed less outward current) channel, whilst drKir2.2a and drKir2.4 were intermediate between the two. In regard to sensitivity to Ba(2+) block, drKir2.4 was the most sensitive (IC50 = 1.8 μM) and drKir2.1a the least sensitive channel (IC50 = 132 μM). These findings indicate that the Kir2 isoform composition of the zebrafish heart markedly differs from that of mammalian hearts. Furthermore orthologous Kir2 channels (Kir2.1 and Kir2.4) of zebrafish and mammals show striking differences in Ba(2+)-sensitivity. Structural and functional differences needs to be taken into account when zebrafish is used as a model for human cardiac electrophysiology, cardiac diseases, and in screening cardioactive substances.
authors.affiliation: Department of Biology, University of Eastern Finland, P.O. Box 111, 80101, Joensuu, Finland. minna.hassinen@uef.fi.
authors.forename: Minna
authors.initials: M
authors.lastname: Hassinen
authors.affiliation: Department of Biology, University of Eastern Finland, P.O. Box 111, 80101, Joensuu, Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Haverinen
authors.affiliation: Faculty of Life Sciences, University of Manchester, 46 Grafton Street, Manchester, M13 9NT, UK.
authors.forename: Matt E
authors.initials: ME
authors.lastname: Hardy
authors.affiliation: Faculty of Life Sciences, University of Manchester, 46 Grafton Street, Manchester, M13 9NT, UK.
authors.forename: Holly A
authors.initials: HA
authors.lastname: Shiels
authors.affiliation: Department of Biology, University of Eastern Finland, P.O. Box 111, 80101, Joensuu, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Vornanen
mesh_terms: D000200:Action Potentials; D000595:Amino Acid Sequence; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002478:Cells, Cultured; D057809:HEK293 Cells; D006325:Heart Atria / Q000166:cytology; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C489461:Kir2.1 channel; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D021122:Protein Subunits; D029961:Zebrafish Proteins; D001464:Barium
keywords: Heart; Inward rectifier potassium current; Kir2 channel; Zebrafish