K+/Na+ hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4)

Function

• hyperpolarization-activated ion channel with very slow activation & inactivation
• exhibits weak selectivity for K+ over Na+
• may contribute to the native pacemaker currents in heart (If) & in neurons (Ih)
• activated by cAMP
• may mediate responses to sour stimuli
• the K+ channel is probably composed of a homo- or heterotetrameric complex of pore-forming subunits

Structure

• the segment S4 is probably the voltage-sensor & is characterized by a series of positively charged amino acids at every third position
• belongs to the K+ channel HCN family
• contains 1 cyclic nucleotide-binding domain

Compartment

membrane

Expression

• highly expressed in thalamus, testis & in heart, both in ventricle & atrium
• detected at much lower levels in amygdala, substantia nigra, cerebellum & hippocampus

Pathology

• defects in HCN4 are a cause of sick sinus syndrome type 2
• defects in HCN4 are the cause of Brugada syndrome type 8

Notes

• inhibited by extracellular Cs+

More general terms

• hyperpolarization-activated cyclic nucleotide gated K+ channel
• transmembrane 6 protein
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=10021
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:10021
• OMIM: https://mirror.omim.org/entry/163800
• OMIM: https://mirror.omim.org/entry/605206
• OMIM: https://mirror.omim.org/entry/613123
• UniProt: http://www.uniprot.org/uniprot/Q9Y3Q4.html