title: Molecular components of transient outward potassium current in cultured neonatal rat ventricular myocytes.
abstract: We have previously reported that K(v1.4), K(v4.2), and K(v4.3) mRNAs are present in adult and neonatal rat ventricular myocytes, and that transient outward potassium current (I(to)) recovers from inactivation with a slow (I(to,s)) and a fast (I(to,f)) time course. This study was designed to determine the molecular correlates of I(to,s) and I(to,f) in cultured neonatal rat ventricular myocytes (NRVM) employing dominant-negative adenoviral infections to manipulate the function of endogenous I(to)-encoding K+ channels. Western blot data from cultured NRVM showed that K(v1.4), K(v4.2), and K(v4.3) channel proteins are present in these myocytes. The biphasic recovery from inactivation of I(to) in control GFP-infected myocytes demonstrated equal contribution of I(to,s) and I(to,f) in NRVM. Infection of cultured NRVM with adenoviruses expressing full-length K(v1.4) or K(v4.2) genes generated currents with recovery from inactivation kinetics similar to native I(to,s) and I(to,f) in GFP-infected myocytes, respectively. Overexpression of dominant-negative truncated K(v1.4) transgene (K(v1.4)N) caused a 51% reduction in I(to), selectively removing the slowly recovering I(to,s). Overexpression of dominant-negative K(v4.2)N reduced I(to) by 53% and eliminated the fast-recovering I(to,f). Our results establish that, in neonatal rat ventricular myocytes, the shaker K(v1) family (probably K(v1.4) and/or K(v1.7)) underlies I(to,s), and that the shal K(v4) family (probably K(v4.2) and K(v4.3)) is responsible for I(to,f).
authors.affiliation: Department of Physiology and Medicine, Heart and Stroke, Richard Lewar Center, and Division of Cardiology, University Health Network, University of Toronto, 150 College St., Toronto, Ontario M5G 3E2, Canada.
authors.forename: Zamaneh
authors.initials: Z
authors.lastname: Kassiri
authors.forename: Roger
authors.initials: R
authors.lastname: Hajjar
authors.forename: Peter H
authors.initials: PH
authors.lastname: Backx
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004594:Electrophysiology / Q000379:methods; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D049452:Green Fluorescent Proteins; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism*; D051665:Kv1.4 Potassium Channel; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D051672:Shal Potassium Channels
chemical_list: C496979:Kcna4 protein, rat; D051665:Kv1.4 Potassium Channel; D008164:Luminescent Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D051672:Shal Potassium Channels; D049452:Green Fluorescent Proteins; D011188:Potassium