Ageing-dependent remodelling of ion channel and Ca2+ clock genes underlying sino-atrial node pacemaking.

Objective: The function of the sinoatrial 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 characterising electrophysiological changes and determining if changes in gene expression are involved. Methods: In young and old rats, SAN function was characterised in the anaesthetised animal, isolated heart and isolated right atrium using ECG and action potential recordings; gene expression was characterised using quantitative PCR. Results: SAN function declined with age: the intrinsic heart rate declined by 18�3%, the corrected SAN recovery time increased by 43�13% and the SAN action potential duration (APD) 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)1.5 and Ca(v)1.2 and decreases in K(v)1.5 and HCN1). Conclusions: 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.