Referenced in: none

Automatically associated channels: Kv1.5

Title: alpha1-adrenoceptor agonists and IGF-1, myocardial hypertrophic factors, regulate the Kv1.5 K+ channel expression differentially in cultured newborn rat ventricular cells.

Authors: W Guo, K Kamiya, K Yasui, I Kodama, J Toyama

Journal, date & volume: Pflugers Arch., 1998 Jun , 436, 26-32

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9560443

Abstract
Interest has arisen concerning the importance of alpha-adrenergic function and insulin-like growth factor-1 (IGF-1) in cardiac remodelling. The hypothesis that these two factors may underlie the regulation of voltage-gated K+ channel expression in hypertrophied cardiomyocytes was tested by performing Western blot analysis of the Kv1.5 K+ channel alpha-subunit in cultured newborn rat ventricular cells. Myocyte size was quantified by surface area and total cell protein concentration. Cell exposure to the alpha1-adrenoceptor agonist phenylephrine (PE, 20 microM) and IGF-1 (60 ng/ml) for 72 h both induced a significant increase of cell size indicating myocyte hypertrophy, which could be separately blocked by the protein kinase C inhibitor staurosporine (20 nM) and the tyrosine kinase inhibitor genistein (15 microM). Western blots of cell proteins prepared from myocyte cultures showed a single protein band at 75 kD recognized by the anti-Kv1.5 antibody, and demonstrated a 56% reduction in the Kv1. 5 immunoreactive protein level in the PE-treated cell preparations. This suppression was not affected by staurosporine, but was remarkably attenuated by W7 (20 microM), a selective calmodulin antagonist. In contrast to PE, a 48% enhancement of the protein expression of Kv1.5 channel was induced by IGF-1 and this stimulation was specifically blocked by genistein. Our findings suggest that the differential regulation of cardiac Kv1.5 K+ channel expression can be produced by alpha1-adrenoceptor activation and IGF-1 via distinctive signalling pathways. Calmodulin-dependent kinase and tyrosine kinase contribute importantly to the alpha1-adrenoceptor-mediated decrease and the IGF-1-mediated increase in cardiac Kv1.5 K+ channel expression, respectively.