title: Ageing-dependent remodelling of ion channel and Ca2+ clock genes underlying sino-atrial node pacemaking.
abstract: 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.
authors: University of Manchester, Manchester M13 9NT, UK.
authors: James O
authors: JO
authors: Tellez
authors: Michal
authors: M
authors: Mczewski
authors: Joseph
authors: J
authors: Yanni
authors: Pavel
authors: P
authors: Sutyagin
authors: Urszula
authors: U
authors: Mackiewicz
authors: Andrew
authors: A
authors: Atkinson
authors: Shin
authors: S
authors: Inada
authors: Andrzej
authors: A
authors: Beresewicz
authors: Rudi
authors: R
authors: Billeter
authors: Halina
authors: H
authors: Dobrzynski
authors: M R
authors: MR
authors: Boyett
mesh_terms: D000200:Action Potentials; D000375:Aging / Q000502:physiology*; D000818:Animals; D016280:Atrial Function, Right / Q000502:physiology; D015220:Calcium Channels / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000502:physiology; D004452:Echocardiography; D006339:Heart Rate; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D010477:Perfusion; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012849:Sinoatrial Node / Q000502:physiology* / Q000503:physiopathology; D015222:Sodium Channels / Q000378:metabolism; D050052:TRPC Cation Channels / Q000502:physiology
chemical_list: D015220:Calcium Channels; D054815:Cyclic Nucleotide-Gated Cation Channels; C578667:Hcn1 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D015222:Sodium Channels; D050052:TRPC Cation Channels