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Expression of the hyperpolarization-activated current, I(f), in cultured adult rat ventricular cardiomyocytes and its modulation by hypertrophic factors

The hyperpolarization-activated, cyclic nucleotide-gated (HCN) current, I(f), is typically overexpressed in myocytes from hypertrophied and failing hearts, where it may play an arrhythmogenic role. Signaling pathways activated by agonists such as angiotensin-II, endothelin-1 and phenylephrine, via G...

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Published in:Pharmacological research 2008-02, Vol.57 (2), p.100-109
Main Authors: Stillitano, Francesca, Sartiani, Laura, DePaoli, Petra, Mugelli, Alessandro, Cerbai, Elisabetta
Format: Article
Language:English
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Summary:The hyperpolarization-activated, cyclic nucleotide-gated (HCN) current, I(f), is typically overexpressed in myocytes from hypertrophied and failing hearts, where it may play an arrhythmogenic role. Signaling pathways activated by agonists such as angiotensin-II, endothelin-1 and phenylephrine, via G protein-coupled receptors (GPCR), promote myocardial hypertrophy, but their effect on cellular electrophysiological remodeling, particularly I(f) expression is largely unknown. Thus, I(f) expression was measured by patch-clamp and quantitative RT-PCR measurement in cultured adult rat ventricular cardiomyocytes (VCM) exposed to different culture conditions, that is, in the absence or presence of: fetal bovine serum (FBS, 5%), 0.1 microM angiotensin-II, 0.1 microM endothelin-1 or 20 microM phenylephrine. Membrane capacitance (C(m)) was used to estimate cell size and current density in patch-clamped VCM. At 8 days of culture, about 60% of VCM showed I(f). In serum-free medium, I(f) density was increased by phenylephrine (2.28+/-0.51 vs. 0.84+/-0.30 pA/pF in CTR, p
ISSN:1043-6618
1096-1186
DOI:10.1016/j.phrs.2007.12.002