Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain

Brain Res Mol Brain Res. 2000 Sep 30;81(1-2):129-39. doi: 10.1016/s0169-328x(00)00155-8.


Rhythmic firing in brain and heart is mediated by pacemaker channels that are activated by hyperpolarization and regulated directly by cyclic nucleotides. Recent work has identified a new gene family that encodes such channels, which are termed hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. In this study, we report the molecular cloning and localization by in situ hybridization of HCN1-4 in adult rat brain. The rat HCN1-4 clones show high homology to the deduced amino acid sequence of the mouse channels (>97% identity). The mRNA expression of the four channels in adult brain was evaluated in a systematic manner from the olfactory bulb to lower brain stem nuclei. Each mRNA demonstrated a unique pattern of distribution. HCN1 expression is highly enriched in cerebral cortex, hippocampus, cerebellum, and facial motor nucleus; HCN2 is highly abundant in mamillary bodies, pontine nucleus, ventral cochlear nucleus, and nucleus of the trapezoid body; HCN3 expression is most pronounced in supraoptic nucleus of hypothalamus; and HCN4 expression is most abundant in medial habenula and anterior and principal relay nuclei of the thalamus. These variations in regional specificity of HCN channels could generate important differences in neuronal pacemaker activity across brain systems.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / metabolism*
  • Brain / physiology*
  • Cloning, Molecular
  • Cyclic Nucleotide-Gated Cation Channels
  • Humans
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • In Situ Hybridization
  • Ion Channels
  • Male
  • Membrane Potentials
  • Models, Molecular
  • Molecular Sequence Data
  • Multigene Family*
  • Muscle Proteins*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Organ Specificity
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Protein Structure, Secondary
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcription, Genetic*


  • Cyclic Nucleotide-Gated Cation Channels
  • HCN1 protein, human
  • HCN2 protein, human
  • HCN3 protein, rat
  • HCN4 protein, human
  • HCN4 protein, rat
  • Hcn1 protein, mouse
  • Hcn1 protein, rat
  • Hcn2 protein, mouse
  • Hcn2 protein, rat
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels
  • Muscle Proteins
  • Nerve Tissue Proteins
  • Potassium Channels
  • RNA, Messenger