| 18156198 |
Walsh KB, Zhang J: Neonatal rat cardiac fibroblasts express three types of voltage-gated K+ channels: regulation of a transient outward current by protein kinase C. Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H1010-7. Epub 2007 Dec 21.
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. |
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