Year: 2006
Type: article
Study design: Observational Study
Abstract: We found that sinus bradycardia in members of a large family was associated with a mutation in the gene coding for the pacemaker HCN4 ion channel. Pacemaker channels of the sinoatrial node generate spontaneous activity and mediate cyclic AMP (cAMP)-dependent autonomic modulation of the heart rate. The mutation associated with bradycardia is located near the cAMP-binding site; functional analysis found that mutant channels respond normally to cAMP but are activated at more negative voltages than are wild-type channels. These changes, which mimic those of mild vagal stimulation, slow the heart rate by decreasing the inward diastolic current. Thus, diminished function of pacemaker channels is linked to familial bradycardia.
Source: New England Journal of Medicine
DOI: 10.1056/nejmoa052475
Institution: University of Milan
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2085774451