title: HCN channels and heart rate.
abstract: Hyperpolarization and Cyclic Nucleotide (HCN) -gated channels represent the molecular correlates of the "funny" pacemaker current (I(f)), a current activated by hyperpolarization and considered able to influence the sinus node function in generating cardiac impulses. HCN channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. This channel family comprises four members: HCN1-4, but there is a general agreement to consider HCN4 as the main isoform able to control heart rate. This review aims to summarize advanced insights into the structure, function and cellular regulation of HCN channels in order to better understand the role of such channels in regulating heart rate and heart function in normal and pathological conditions. Therefore, we evaluated the possible therapeutic application of the selective HCN channels blockers in heart rate control.
authors.affiliation: Section of Cardiovascular Diseases, Department of Emergency and Organ Transplantation, University of Bari, School of Medicine, Policlinico, Bari 70124, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Scicchitano
authors.forename: Santa
authors.initials: S
authors.lastname: Carbonara
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ricci
authors.forename: Cosimo
authors.initials: C
authors.lastname: Mandurino
authors.forename: Manuela
authors.initials: M
authors.lastname: Locorotondo
authors.forename: Gabriella
authors.initials: G
authors.lastname: Bulzis
authors.forename: Michele
authors.initials: M
authors.lastname: Gesualdo
authors.forename: Annapaola
authors.initials: A
authors.lastname: Zito
authors.forename: Rosa
authors.initials: R
authors.lastname: Carbonara
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dentamaro
authors.forename: Graziano
authors.initials: G
authors.lastname: Riccioni
authors.forename: Marco Matteo
authors.initials: MM
authors.lastname: Ciccone
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000235:genetics; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D049990:Membrane Transport Modulators / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology
chemical_list: D002317:Cardiovascular Agents; D054815:Cyclic Nucleotide-Gated Cation Channels; D049990:Membrane Transport Modulators