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• W1993545434 abstract "Hyperpolarization-activated, cyclic nucleotide sensitive (HCN) channels underlie the pacemaker current I(f), which plays an essential role in spontaneous cardiac activity. HCN channel subunits (HCN1-4) are believed to be modulated by additional regulatory proteins, which still have to be identified. Using biochemistry, molecularbiology and electrophysiology methods we demonstrate a protein-protein interaction between HCN2 and the K(+) channel regulator protein 1, named KCR1. In coimmunoprecipitation experiments we show that KCR1 and HCN2 proteins are able to associate. Heterologously expressed HCN2 whole-cell current density was significantly decreased by KCR1. KCR1 profoundly suppressed I(HCN2) single-channel activity, indicating a functional interaction between KCR1 and the HCN2 channel subunit. Endogenous KCR1 expression could be detected in adult and neonatal rat ventriculocytes. Adenoviral-mediated overexpression of KCR1 in rat cardiomyocytes (i) reduced I(f) whole-cell currents, (ii) suppressed most single-channel gating parameters, (iii) altered the activation kinetics, (iv) suppressed spontaneous action potential activity, and (v) the beating rate. More importantly, siRNA-based knock-down of endogenous KCR1 increased the native I(f) current size and single-channel activity and accelerated spontaneous beating rate, supporting an inhibitory action of endogenous KCR1 on native I(f). Our observations demonstrate for the first time that KCR1 modulates I(HCN2)/I(f) channel gating and indicate that KCR1 serves as a regulator of cardiac automaticity." @default.
• W1993545434 created "2016-06-24" @default.
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• W1993545434 date "2008-01-30" @default.
• W1993545434 modified "2023-09-27" @default.
• W1993545434 title "K+ Channel Regulator KCR1 Suppresses Heart Rhythm by Modulating the Pacemaker Current If" @default.
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• W1993545434 doi "https://doi.org/10.1371/journal.pone.0001511" @default.
• W1993545434 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2204056" @default.
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• W1993545434 hasPublicationYear "2008" @default.
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