Encyclopedia of Molecular Pharmacology

Living Edition
| Editors: Stefan Offermanns, Walter Rosenthal

HCN Channels

  • M. BielEmail author
  • V. Hammelmann
  • S. Fenske
Living reference work entry
DOI: https://doi.org/10.1007/978-3-030-21573-6_10015-1


Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization. Cyclic nucleotides enhance HCN channel activity by affecting the voltage dependence of channel activation (Biel et al. 2009).

Basic Characteristics

A cation current that slowly activates upon membrane hyperpolarization was detected in a variety of excitable cells including neurons and cardiac pacemaker cells in the late 1970s and early 1980s. This current is inwardly directed at the physiological resting membrane potentials of most cells and is carried by Na+ and K+ ions and, hence, depolarizes the cell membrane. Additionally, cyclic adenosine monophosphate (cAMP) was found to facilitate current activation in a direct, PKA-independent manner. Because of these unique biophysical properties, this current was termed funny current (If) in the heart or hyperpolarization-activated current (Ih) in the brain.

HCN channels represent the molecular correlate of the Ih/If...

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  1. Biel M, Wahl-Schott C, Michalakis S et al (2009) Hyperpolarization-activated cation channels: from genes to function. Physiol Rev 89:847–885CrossRefGoogle Scholar
  2. Dai G, Aman TK, Dimaio F et al (2019) The HCN channel voltage sensor undergoes a large downward motion during hyperpolarization. Nat Struct Mol Biol 26:686CrossRefGoogle Scholar
  3. Hammelmann V, Stieglitz MS, Hulle H et al (2019) Abolishing cAMP sensitivity in HCN2 pacemaker channels induces generalized seizures. JCI Insight 4:126418CrossRefGoogle Scholar
  4. Prescribing Information CORLANOR® (ivabradine) tablets, for oral use, version 04/2019. Amgen, Thousand OaksGoogle Scholar
  5. Yu FH, Yarov-Yarovoy V, Gutman GA et al (2005) Overview of molecular relationships in the voltage-gated ion channel superfamily. Pharmacol Rev 57:387–395CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Center for Drug Research, Department of PharmacyLudwig-Maximilians UniversityMunichGermany