Aim: 

With age, the function of the sinoatrial node (SAN) deteriorates and the incidence of SAN dysfunction increases. The aim of the study was to investigate why.

Methods: 

SAN/atrial preparations from 3-month-old (n = 12) and 24-month-old (n = 10) rats were compared using electrophysiology, immunohistochemistry and quantitative PCR (qPCR).

Results: 

In young rats, the position of the leading pacemaker site was significantly more superior and the intrinsic heart rate was significantly faster (20%). 2 mM Cs⁺ (blocker of HCN4 responsible for pacemaker current, If) caused a significantly smaller increase in cycle length in young (22 ± 5%) than in old (44 ± 10%) rats. 100 nM TTX (blocker of Na_v1.1 responsible for TTX-sensitive Na⁺ current) caused an increase in cycle length in young rats (5 ± 2%), but a decrease in old rats (9 ± 3%); subsequent addition of 2 mM TTX (blocker of Na_v1.5 responsible for TTX-resistant Na⁺ current) caused a significantly smaller increase in cycle length in young (11 ± 3%) than in old (37 ± 11%) rats. At protein and mRNA levels, HCN4 was present in the SAN but not atrial muscle, Na_v1.1 was present in both the SAN and atrial muscle, and Na_v1.5 was absent from the SAN but present in the atrial muscle. In young as compared to old rats, there was significantly more Nav1.1 mRNA in the SAN and significantly less Na_v1.5 mRNA in the atrial muscle. Furthermore, the volume of HCN4-positive/Na_v1.5-negative SAN tissue increased significantly (by 97%) from young to old rats.

Conclusion: 

With age, changes in the electrophysiology of the SAN result from changes in ion channels.