Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 (IPR030173)

Short name: HCN4

Overlapping homologous superfamilies


Family relationships


This entry represents HCN4, which belongs to the hyperpolarisation-activated cyclic nucleotide-gated (HCN) channel family. It is the major HCN channel isoform detected in heart and in the atrioventricular node [PMID: 18953682]. It is required for the formation of adult pacemaker cells during embryonic heart development and for the cAMP-dependent up-regulation of embryonic heart rate. It is also strongly expressed in some parts of the brain, such the thalamic nuclei and the mitral cell layer of the olfactory bulb [PMID: 18953682, PMID: 14991560].

The hyperpolarisation-activated cation current (termed I(f), I(h), or I(q)) plays a key role in the initiation and modulation of cardiac and neuronal pacemaker depolarisations. This current is carried by both K+ and Na+ through I(h) or I(f) channels, such as members of the hyperpolarisation-activated cyclic nucleotide-gated (HCN) family. HCN channels belong to the superfamily of voltage-gated pore loop channels. The voltage-dependent opening of the HCN channels is directly regulated by the binding of cAMP. In vertebrates, the HCN channel family comprises four members (HCN1-4) [PMID: 12161074]. Whereas HCN3 seems to be specifically expressed in neurons, the other three channels (HCN1, 2, and 4) have been detected in both heart and brain [PMID: 9634236, PMID: 11248683]. HCN channels contain six membrane-spanning helices (S1-S6), including a positively charged voltage-sensing S4 segment and an ion-conducting pore between S5 and S6. In the C terminus the channels carry a cyclic nucleotide-binding domain (CNBD) [PMID: 12161074]. Binding of cAMP to the CNBD speeds up channel opening and shifts the voltage-dependence of activation to more positive voltages [PMID: 18953682]. HCN channels exhibit weak selectivity for potassium over sodium ions.

GO terms

Biological Process

GO:0006813 potassium ion transport
GO:0002027 regulation of heart rate
GO:0006814 sodium ion transport

Molecular Function

GO:0030552 cAMP binding
GO:0005249 voltage-gated potassium channel activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.