Cardiac HCN channels: structure, function, and modulation

Trends Cardiovasc Med. 2002 Jul;12(5):206-12. doi: 10.1016/s1050-1738(02)00162-7.


The hyperpolarization-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 depolarizations. Recently, the hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channel subunits has been identified by molecular cloning. When heterologously expressed, each of the four HCN subunits (HCN1-4) generates channels with the principal properties of native I(f), indicating that HCN channels are the molecular correlate of this current. This review describes the molecular and functional diversity of the HCN channel family. The structural determinants of channel activation, modulation, and ion permeation are discussed. The expression pattern of HCN channels in different heart regions is reviewed. Finally, the relationships between biophysical properties of cloned HCN channel types and native cardiac I(f) are explored.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cyclic Nucleotide-Gated Cation Channels
  • Heart / physiology*
  • Humans
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels / chemistry
  • Ion Channels / physiology*
  • Mice
  • Molecular Sequence Data
  • Myocardium / metabolism
  • Nerve Tissue Proteins*
  • Potassium Channels
  • Rabbits
  • Rats


  • Cyclic Nucleotide-Gated Cation Channels
  • HCN1 protein, human
  • Hcn1 protein, mouse
  • Hcn1 protein, rat
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels
  • Nerve Tissue Proteins
  • Potassium Channels