Premium
Ageing‐dependent remodelling of ion channel and Ca 2+ clock genes underlying sino‐atrial node pacemaking
Author(s) -
Tellez James O.,
Mączewski Michal,
Yanni Joseph,
Sutyagin Pavel,
Mackiewicz Urszula,
Atkinson Andrew,
Inada Shin,
Beresewicz Andrzej,
Billeter Rudi,
Dobrzynski Halina,
Boyett M. R.
Publication year - 2011
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2011.057752
Subject(s) - ageing , medicine , repolarization , gene expression , ion channel , endocrinology , sinoatrial node , electrophysiology , heart rate , ryanodine receptor 2 , cardiology , gene , chemistry , biology , calcium , genetics , ryanodine receptor , receptor , blood pressure
The function of the sino‐atrial node (SAN), the pacemaker of the heart, is known to decline with age, resulting in pacemaker disease in the elderly. The aim of the study was to investigate the effects of ageing on the SAN by characterizing electrophysiological changes and determining whether changes in gene expression are involved. In young and old rats, SAN function was characterized in the anaesthetized animal, isolated heart and isolated right atrium using ECG and action potential recordings; gene expression was characterized using quantitative PCR. The SAN function declined with age as follows: the intrinsic heart rate declined by 18 ± 3%; the corrected SAN recovery time increased by 43 ± 13%; and the SAN action potential duration increased by 11 ± 3% (at 75% repolarization). Gene expression in the SAN changed considerably with age, e.g. there was an age‐dependent decrease in the Ca 2+ clock gene, RYR2, and changes in many ion channels (e.g. increases in Na v 1.5, Na v β1 and Ca v 1.2 and decreases in K v 1.5 and HCN1). In conclusion, with age, there are changes in the expression of ion channel and Ca 2+ clock genes in the SAN, and the changes may provide a partial explanation for the age‐dependent decline in pacemaker function.