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 I-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.
The cardiac pacemaker current / M. Baruscotti, A. Barbuti, A. Bucchi. - In: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY. - ISSN 0022-2828. - 48:1(2010), pp. 55-64.
|Titolo:||The cardiac pacemaker current|
BARUSCOTTI, MIRKO (Primo)
BARBUTI, ANDREA FRANCESCO (Secondo)
BUCCHI, ANNALISA (Ultimo)
|Parole Chiave:||Pacemaker current ; SAN ; HCN clones ; HCN knockout mice ; HCN-associated pathologies|
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
|Data di pubblicazione:||2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.yjmcc.2009.06.019|
|Appare nelle tipologie:||01 - Articolo su periodico|