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α1-Adrenoceptor agonists and IGF-1, myocardial hypertrophic factors, regulate the Kv1.5 K+ channel expression differentially in cultured newborn rat ventricular cells

α1-Adrenoceptor agonists and IGF-1, myocardial hypertrophic factors, regulate the Kv1.5 K+...  Interest has arisen concerning the importance of α-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 α-subunit in cultured newborn rat ventricular cells. Myocyte size was quantified by surface area and total cell protein concentration. Cell exposure to the α1-adrenoceptor agonist phenylephrine (PE, 20 μM) 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 μM). 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 μM), 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 α1-adrenoceptor activation and IGF-1 via distinctive signalling pathways. Calmodulin-dependent kinase and tyrosine kinase contribute importantly to the α1-adrenoceptor-mediated decrease and the IGF-1-mediated increase in cardiac Kv1.5 K+ channel expression, respectively. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Pflügers Archiv European Journal of Physiologyl of Physiology Springer Journals

α1-Adrenoceptor agonists and IGF-1, myocardial hypertrophic factors, regulate the Kv1.5 K+ channel expression differentially in cultured newborn rat ventricular cells

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References (22)

Publisher
Springer Journals
Copyright
Copyright © 1998 by Springer-Verlag Berlin Heidelberg
Subject
Biomedicine; Human Physiology; Molecular Medicine; Neurosciences; Cell Biology; Receptors
ISSN
0031-6768
eISSN
1432-2013
DOI
10.1007/s004240050600
Publisher site
See Article on Publisher Site

Abstract

 Interest has arisen concerning the importance of α-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 α-subunit in cultured newborn rat ventricular cells. Myocyte size was quantified by surface area and total cell protein concentration. Cell exposure to the α1-adrenoceptor agonist phenylephrine (PE, 20 μM) 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 μM). 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 μM), 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 α1-adrenoceptor activation and IGF-1 via distinctive signalling pathways. Calmodulin-dependent kinase and tyrosine kinase contribute importantly to the α1-adrenoceptor-mediated decrease and the IGF-1-mediated increase in cardiac Kv1.5 K+ channel expression, respectively.

Journal

Pflügers Archiv European Journal of Physiologyl of Physiology – Springer Journals

Published: Apr 27, 1998

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