Cellular context and multiple channel domains determine cAMP sensitivity of HCN4 channels: Ligand-independent relief of autoinhibition in HCN4

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Cellular context and multiple channel domains determine cAMP sensitivity of HCN4 channels: Ligand-independent relief of autoinhibition in HCN4

Hyperpolarization-activated, cyclic nucleotide-sensitive (HCN) channels produce the I(f) and I(h) currents, which are critical for cardiac pacemaking and neuronal excitability, respectively. HCN channels are modulated by cyclic AMP (cAMP), which binds to a conserved cyclic nucleotide-binding domain (CNBD) in the C terminus. The unliganded CNBD has been shown to inhibit voltage-dependent gating ...

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Proteolytic processing of HCN2 and co-assembly with HCN4 in the generation of cardiac pacemaker channels.

In sino-atrial and atrio-ventricular nodal cells, hyperpolarization-activated cyclic nucleotide-gated (HCN) inward current carrying cationic channels, I(f), are expressed that contribute importantly to the diastolic depolarization critical for cardiac pacemaker activity. Although previous studies have demonstrated myocardial expression of both the HCN2 and HCN4 subunits, the specific roles of t...

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ژورنال

عنوان ژورنال: Journal of General Physiology

سال: 2012

ISSN: 1540-7748,0022-1295

DOI: 10.1085/jgp.201210858