Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 (IPR030169)

Short name: K/Na_HCN1

Overlapping homologous superfamilies


Family relationships


This entry represents HCN1, which belongs to the hyperpolarisation-activated cyclic nucleotide-gated (HCN) channel family. HCN1 is expressed in the brain, spinal cord, dorsal root ganglion and heart muscle [PMID: 18953682]. It contributes to the native pacemaker currents in heart and in neurons [PMID: 15351778, PMID: 9630217, PMID: 11459060]. It may be involved in motor learning and hippocampal-dependent network oscillation in mice [PMID: 14651847, PMID: 15550252]. It binds to filaminA, a putative cytoplasmic scaffold protein that binds actin and links transmembrane proteins, such as the K+ channels Kv4.2 and Kir2.1, to the actin cytoskeleton [PMID: 15292205, PMID: 11102480, PMID: 12923176].

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:0071805 potassium ion transmembrane transport
GO:0035725 sodium ion transmembrane transport

Molecular Function

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

Cellular Component

GO:0005887 integral component of plasma membrane

Contributing signatures

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