TY - JOUR
T1 - Genetics of sinoatrial node function and heart rate disorders
AU - van der Maarel, Lieve E.
AU - Postma, Alex V.
AU - Christoffels, Vincent M.
N1 - Funding Information: This work was supported by Nederlandse Organisatie voor Wetenschappelijk Onderzoek (OCENW.GROOT.2019.029). Publisher Copyright: © 2023 Company of Biologists Ltd. All rights reserved.
PY - 2023/5/1
Y1 - 2023/5/1
N2 - The sinoatrial node (SAN) is the primary pacemaker of the mammalian heart, initiating its electrical activation and ensuring that the heart's functional cardiac output meets physiological demand. SAN dysfunction (SND) can cause complex cardiac arrhythmias that can manifest as severe sinus bradycardia, sinus arrest, chronotropic incompetence and increased susceptibility to atrial fibrillation, among other cardiac conditions. SND has a complex aetiology, with both pre-existing disease and heritable genetic variation predisposing individuals to this pathology. In this Review, we summarize the current understanding of the genetic contributions to SND and the insights that they provide into this disorder's underlying molecular mechanisms. With an improved understanding of these molecular mechanisms, we can improve treatment options for SND patients and develop new therapeutics.
AB - The sinoatrial node (SAN) is the primary pacemaker of the mammalian heart, initiating its electrical activation and ensuring that the heart's functional cardiac output meets physiological demand. SAN dysfunction (SND) can cause complex cardiac arrhythmias that can manifest as severe sinus bradycardia, sinus arrest, chronotropic incompetence and increased susceptibility to atrial fibrillation, among other cardiac conditions. SND has a complex aetiology, with both pre-existing disease and heritable genetic variation predisposing individuals to this pathology. In this Review, we summarize the current understanding of the genetic contributions to SND and the insights that they provide into this disorder's underlying molecular mechanisms. With an improved understanding of these molecular mechanisms, we can improve treatment options for SND patients and develop new therapeutics.
KW - Arrhythmia
KW - Genetics
KW - Sinoatrial node
UR - http://www.scopus.com/inward/record.url?scp=85159484254&partnerID=8YFLogxK
U2 - https://doi.org/10.1242/dmm.050101
DO - https://doi.org/10.1242/dmm.050101
M3 - Review article
C2 - 37194974
SN - 1754-8403
VL - 16
JO - Disease models & mechanisms
JF - Disease models & mechanisms
IS - 5
M1 - dmm050101
ER -