Neonatal rat cardiac fibroblasts express three types of voltage-gated K+ channels: regulation of a transient outward current by protein kinase C.
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.
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
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