A family of hyperpolarization-activated mammalian cation channels

Nature. 1998 Jun 11;393(6685):587-91. doi: 10.1038/31255.


Pacemaker activity of spontaneously active neurons and heart cells is controlled by a depolarizing, mixed Na+/K+ current, named Ih (or I(f) in the sinoatrial node of the heart). This current is activated on hyperpolarization of the plasma membrane. In addition to depolarizing pacemaker cells, Ih is involved in determining the resting membrane potential of neurons and provides a mechanism to limit hyperpolarizing currents in these cells. Hormones and neurotransmitters that induce a rise in cyclic AMP levels increase Ih by a mechanism that is independent of protein phosphorylation, and which involves direct binding of the cyclic nucleotide to the channel that mediates Ih. Here we report the molecular cloning and functional expression of the gene encoding a hyperpolarization-activated cation channel (HAC1) that is present in brain and heart. This channel exhibits the general properties of Ih channels. We have also identified full-length sequences of two related channels, HAC2 and HAC3, that are specifically expressed in the brain, indicating the existence of a family of hyperpolarization-activated cation channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain Chemistry*
  • Cations
  • Cloning, Molecular
  • Cyclic AMP / metabolism
  • Cyclic Nucleotide-Gated Cation Channels
  • Electrochemistry
  • Humans
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels / analysis*
  • Ion Channels / chemistry
  • Ion Channels / genetics
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Myocardium / chemistry*
  • Nerve Tissue Proteins*
  • Potassium Channels
  • Sequence Homology, Amino Acid


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

Associated data

  • GENBANK/AJ225122
  • GENBANK/AJ225123
  • GENBANK/AJ225124