Does the crista terminalis possess a key role in the elevated risk of arrhythmogenic episodes in the elderly population?

37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCB021

Poster Communications: Does the crista terminalis possess a key role in the elevated risk of arrhythmogenic episodes in the elderly population?

F. S. Hatch1, M. K. Lancaster2, S. A. Jones1

1. University of Hull, Hull, United Kingdom. 2. University of Leeds, Leeds, United Kingdom.

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We have previously reported changes in intracellular calcium handling and associated protein expression within the sinoatrial node (SAN) during ageing (Hatch et al, 2012; Jones et al, 2007). It is however unknown whether other parts of the conduction pathway within the atria, specifically the crista terminalis (CT) and right atrial (RA) muscle itself undergo similar changes. Implicated in atrial arrhythmia generation, changes in the properties of the CT may predispose to ectopic activity and arrhythmias such as atrial fibrillation. Therefore, our study examined the expression of calcium handling proteins across the right atria including the SAN and CT. Male Wistar rats at the ages of 6 months (young) and 24 months (old) (n=5) were sacrificed by intraperitoneal anaesthetic overdose of pentobarbital. The right atrium was removed and dissected to isolate the CT, SAN and RA muscle. Western blot and immunocytochemistry were used to examine the protein expression of sarcoendoplasmic reticulum Ca2+ ATPase pump (SERCA2a), phospholamban (PLB), ryanodine receptors (RYR2), L-type calcium channels (Cav1.2) and the sodium-calcium exchanger (NCX1). Data are presented as mean±SEM, assessed by t-test or two-way ANOVA as appropriate. Ethical approval was given by the University of Hull. When compared with the RA in the young animal; the CT consistently exhibited reduced expression of all calcium-regulatory proteins studied, whilst the SAN possessed reduced protein levels of RYR2 and NCX1. Ageing significantly decreased Cav1.2 protein expression by 40.3±2.6% in the SAN from old animals (p=0.009), but conversely in the CT ageing increased of Cav1.2 expression (64.4±3.9%; p=0.011). Similarly with age RYR2 protein levels fell by 32.0±0.2% within the SAN (p=0.03), but rose by 63.8±5.0% (p<0.001) in the CT from old animals. By contrast NCX1 expression remained the same for both ages in the CT, but was up-regulated by 72±13.5% in the aged SAN (p=0.009). SERCA2a regulation was assessed by the ratio of SERCA2a to monomeric PLB. In young animals there was no significant difference in the ratio across the SAN, CT or RA. Ageing evoked a significant decline in the ratio, 29±8.5% within the SAN and a larger reduction of 40±8.5% in the CT (p<0.001). In contrast, there was a non-significant drop of 12±4.5% in the RA. In conclusion ageing had heterogeneous effects on the expression of calcium regulatory proteins across the right atria. The loss of calcium influx and release channels in the SAN is likely to lead to a reduction in the ability of the pacemaker to operate, despite a potential counter-effect of increasing NCX. In contrast the changes in the CT may increase the likelihood to form an ectopic pacemaker, destabilising the atria and increasing susceptibility to arrhythmias in old age.



Where applicable, experiments conform with Society ethical requirements.

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