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Hyperpolarization-activated cation channels: from genes to function.
Physiol Rev. 2009 Jul; 89(3):847-85.PR

Abstract

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a small subfamily of proteins within the superfamily of pore-loop cation channels. In mammals, the HCN channel family comprises four members (HCN1-4) that are expressed in heart and nervous system. The current produced by HCN channels has been known as I(h) (or I(f) or I(q)). I(h) has also been designated as pacemaker current, because it plays a key role in controlling rhythmic activity of cardiac pacemaker cells and spontaneously firing neurons. Extensive studies over the last decade have provided convincing evidence that I(h) is also involved in a number of basic physiological processes that are not directly associated with rhythmicity. Examples for these non-pacemaking functions of I(h) are the determination of the resting membrane potential, dendritic integration, synaptic transmission, and learning. In this review we summarize recent insights into the structure, function, and cellular regulation of HCN channels. We also discuss in detail the different aspects of HCN channel physiology in the heart and nervous system. To this end, evidence on the role of individual HCN channel types arising from the analysis of HCN knockout mouse models is discussed. Finally, we provide an overview of the impact of HCN channels on the pathogenesis of several diseases and discuss recent attempts to establish HCN channels as drug targets.

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Authors+Show Affiliations

Biel M
Center for Integrated Protein Science CIPS-M and Zentrum für Pharmaforschung, Department Pharmazie, Pharmakologie für Naturwissenschaften, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, Munich D-81377, Germany. mbiel@cup.uni-muenchen.de
Wahl-Schott C
No affiliation info available
Michalakis S
No affiliation info available
Zong X
No affiliation info available

MeSH

Amino Acid SequenceAnimalsChannelopathiesCyclic Nucleotide-Gated Cation ChannelsDisease Models, AnimalHeartHumansHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsIon Channel GatingMiceMice, KnockoutMolecular Sequence DataNervous System Physiological PhenomenaPotassium Channels

Pub Type(s)

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

Language

eng

PubMed ID

19584315

Citation

Biel, Martin, et al. "Hyperpolarization-activated Cation Channels: From Genes to Function." Physiological Reviews, vol. 89, no. 3, 2009, pp. 847-85.
Biel M, Wahl-Schott C, Michalakis S, et al. Hyperpolarization-activated cation channels: from genes to function. Physiol Rev. 2009;89(3):847-85.
Biel, M., Wahl-Schott, C., Michalakis, S., & Zong, X. (2009). Hyperpolarization-activated cation channels: from genes to function. Physiological Reviews, 89(3), 847-85. https://doi.org/10.1152/physrev.00029.2008
Biel M, et al. Hyperpolarization-activated Cation Channels: From Genes to Function. Physiol Rev. 2009;89(3):847-85. PubMed PMID: 19584315.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hyperpolarization-activated cation channels: from genes to function. AU - Biel,Martin, AU - Wahl-Schott,Christian, AU - Michalakis,Stylianos, AU - Zong,Xiangang, PY - 2009/7/9/entrez PY - 2009/7/9/pubmed PY - 2009/8/21/medline SP - 847 EP - 85 JF - Physiological reviews JO - Physiol Rev VL - 89 IS - 3 N2 - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a small subfamily of proteins within the superfamily of pore-loop cation channels. In mammals, the HCN channel family comprises four members (HCN1-4) that are expressed in heart and nervous system. The current produced by HCN channels has been known as I(h) (or I(f) or I(q)). I(h) has also been designated as pacemaker current, because it plays a key role in controlling rhythmic activity of cardiac pacemaker cells and spontaneously firing neurons. Extensive studies over the last decade have provided convincing evidence that I(h) is also involved in a number of basic physiological processes that are not directly associated with rhythmicity. Examples for these non-pacemaking functions of I(h) are the determination of the resting membrane potential, dendritic integration, synaptic transmission, and learning. In this review we summarize recent insights into the structure, function, and cellular regulation of HCN channels. We also discuss in detail the different aspects of HCN channel physiology in the heart and nervous system. To this end, evidence on the role of individual HCN channel types arising from the analysis of HCN knockout mouse models is discussed. Finally, we provide an overview of the impact of HCN channels on the pathogenesis of several diseases and discuss recent attempts to establish HCN channels as drug targets. SN - 0031-9333 UR - https://www.unboundmedicine.com/medline/citation/19584315/Hyperpolarization_activated_cation_channels:_from_genes_to_function_ L2 - https://journals.physiology.org/doi/10.1152/physrev.00029.2008?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -