title: The cardiac pacemaker current.
abstract: In mammals cardiac rate is determined by the duration of the diastolic depolarization of sinoatrial node (SAN) cells which is mainly determined by the pacemaker I(f) current. f-channels are encoded by four members of the hyperpolarization-activated cyclic nucleotide-gated gene (HCN1-4) family. HCN4 is the most abundant isoform in the SAN, and its relevance to pacemaking has been further supported by the discovery of four loss-of-function mutations in patients with mild or severe forms of cardiac rate disturbances. Due to its selective contribution to pacemaking, the I(f) current is also the pharmacological target of a selective heart rate-reducing agent (ivabradine) currently used in the clinical practice. Albeit to a minor extent, the I(f) current is also present in other spontaneously active myocytes of the cardiac conduction system (atrioventricular node and Purkinje fibres). In working atrial and ventricular myocytes f-channels are expressed at a very low level and do not play any physiological role; however in certain pathological conditions over-expression of HCN proteins may represent an arrhythmogenic mechanism. In this review some of the most recent findings on f/HCN channels contribution to pacemaking are described.
authors: Department of Biomolecular Sciences and Biotechnology, Laboratory of Molecular Physiology and Neurobiology, Università degli Studi di Milano, Centro Interuniversitario di Medicina Molecolare e Biofisica Applicata (CIMMBA), via Celoria 26, 20133 Milano, Italy. mirko.baruscotti@unimi.it
authors: Mirko
authors: M
authors: Baruscotti
authors: Andrea
authors: A
authors: Barbuti
authors: Annalisa
authors: A
authors: Bucchi
mesh_terms: D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000378:metabolism*; D006339:Heart Rate / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D012849:Sinoatrial Node / Q000378:metabolism
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels