title: Neonatal rat cardiac fibroblasts express three types of voltage-gated K+ channels: regulation of a transient outward current by protein kinase C.
abstract: Cardiac fibroblasts regulate myocardial development via mechanical, chemical, and electrical interactions with associated cardiomyocytes. The goal of this study was to identify and characterize voltage-gated K(+) (Kv) channels in neonatal rat ventricular fibroblasts. With the use of the whole cell arrangement of the patch-clamp technique, three types of voltage-gated, outward K(+) currents were measured in the cultured fibroblasts. The majority of cells expressed a transient outward K(+) current (I(to)) that activated at potentials positive to -40 mV and partially inactivated during depolarizing voltage steps. I(to) was inhibited by the antiarrhythmic agent flecainide (100 microM) and BaCl(2) (1 mM) but was unaffected by 4-aminopyridine (4-AP; 0.5 and 1 mM). A smaller number of cells expressed one of two types of kinetically distinct, delayed-rectifier K(+) currents [I(K) fast (I(Kf)) and I(K) slow (I(Ks))] that were strongly blocked by 4-AP. Application of phorbol 12-myristate 13-acetate, to stimulate protein kinase C (PKC), inhibited I(to) but had no effect on I(Kf) and I(Ks). Immunoblot analysis revealed the presence of Kv1.4, Kv1.2, Kv1.5, and Kv2.1 alpha-subunits but not Kv4.2 or Kv1.6 alpha-subunits in the fibroblasts. Finally, pretreatment of the cells with 4-AP inhibited angiotensin II-induced intracellular Ca(2+) mobilization. Thus neonatal cardiac fibroblasts express at least three different Kv channels that may contribute to electrical/chemical signaling in these cells.
authors.affiliation: Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina, School of Medicine, Columbia, SC 29208, USA. walsh@med.sc.edu
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Walsh
authors.forename: Jining
authors.initials: J
authors.lastname: Zhang
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D004594:Electrophysiology; D005347:Fibroblasts / Q000502:physiology*; D005424:Flecainide / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D009206:Myocardium / Q000166:cytology*; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000096:biosynthesis / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D024642:Potassium Channels, Voltage-Gated; D000804:Angiotensin II; D015761:4-Aminopyridine; D011493:Protein Kinase C; D005424:Flecainide; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium