HCN Channels

Supporting information

HCN (hyperpolarization-activated, cyclic nucleotide-gated) channels are members of the cyclic nucleotide-regulated channel family along with cyclic nucleotide-gated (CNG) channels. Each channel is made up of four subunits, with each subunit comprising six transmembrane α-helical segments, with the S4 segment thought to be the voltage sensor. They are cation permeable channels that open under hyperpolarization. In contrast to most voltage-gated ion channels, they are constitutively open at voltages near the resting membrane potential, so influence neuronal excitability, synaptic potential integration and neurotransmitter release. They are also gated by cyclic nucleotides, cAMP and cGMP, which enhance channel activity. There are four HCN isoforms, HCN1, 2, 3 and 4, which vary in their biophysical properties and in their expression levels across the heart and central nervous system; HCN1 is the fastest activating, while HCN4 is the slowest activating form. The C-terminus of the channel contains a cyclic-nucleotide binding domain where cyclic nucleotides confer their regulation.

The HCN channel current (Ih or If) is found in neurons, cardiac pacemaker cells and photoreceptors. In cardiac pacemaker cells the (If) current is known to control heart rate. HCN4 is the major isoform found in the adult sinoatrial node and in humans HCN4 mutations are associated with idiopathic sinus bradycardia and arrhythmias. In neurons HCN channels set the resting potential and contribute to neuronal pacemaking. Ih is activated following the end of the action potential and depolarizes the cell to initiate the next action potential. They contribute to mechanisms of epilepsy and pain.

To view external sources of pharmacological information for HCN Channels, please click here: IUPHAR Receptor Code and BJP Guide

View all products for HCN Channels »
Gene Species Gene Symbol Gene Accession No. Protein Accession No.
HCN1 Human HCN1 NM_021072   O60741
Mouse Hcn1 NM_010408 NP_034538
Rat Hcn1 NM_053375 Q9JKB0
HCN2 Human HCN2 NM_001194   Q9UL51
Mouse Hcn2 NM_008226 NP_032252
Rat Hcn2 NM_053684 Q9JKA9
View all HCN Gene Data »

Literature for HCN Channels

Pain Research Product Guide

A collection of over 250 products for pain research, the guide includes research tools for the study of:

  • Nociception
  • Ion Channels
  • G-Protein-Coupled Receptors
  • Intracellular Signaling
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Pain Research Product Guide
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Cardiovascular disease remains one of the major causes of morbidity and mortality in the Western world and therefore this therapeutic area continues to be of great interest to researchers. This poster highlights the key GPCRs regulating vascular reactivity.

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Cardiovascular Life Science Poster
Pain Life Science Poster

Written by Grant D. Nicol and Michael R. Vasko, this poster outlines the excitatory and inhibitory signaling pathways involved in modulation of peripheral sensitization. The role of ion channels, GPCRs, neurotrophins, and cytokines in sensory neurons are also described. Compounds available from Tocris are listed.

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Pain Life Science Poster

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Pain Research Product Guide

Pain Research Product Guide

Our Pain guide highlights over 280 products for Pain research. Request copy or view PDF today.

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Regulation of Vascular Reactivity by GPCRs

Written by J.J. Maguire and A.P. Davenport

Cardiovascular Life Science Poster

Our Cardiovascular poster highlights the key G protein-coupled receptors involved in the regulation of vascular reactivity. Request copy today.

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Peripheral Sensitization

Written by Grant D. Nicol and Michael R. Vasko

Pain Life Science Poster

Our Peripheral Sensitization poster gives a summary of the excitatory and inhibitory signaling pathways involved in modulation of peripheral sensitization. Request copy or view PDF today.

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