Key result
Adenovirus-mediated gene transfer of HCN2 and HCN212 significantly increased the pacemaker rate of rat subsidiary atrial pacemaker tissue close to that of the native sinoatrial node.
Why the study?
Does HCN over-expression accelerate the pacemaker rate of subsidiary atrial pacemaker tissue in rats?
Does HCN over-expression accelerate the pacemaker rate of subsidiary atrial pacemaker tissue in rats?
Over-expression of HCN2 or HCN212 can accelerate the pacing rate of subsidiary atrial pacemaker tissue, providing proof of concept for biopacemaking in sick sinus syndrome.
AIMS: Although the right atrium (RA contains subsidiary atrial pacemaker (SAP) tissue that can take over from the sinoatrial node (SAN) in sick sinus syndrome (SSS), SAP tissue is bradycardic. Little is known about SAP tissue and one aim of the study was to characterize ion channel expression to obtain insight into SAP pacemaker mechanisms. A second aim was to determine whether HCN over-expression (a 'biopacemaker'-like strategy) can accelerate the pacemaker rate producing a pacemaker that is similar in nature to the SAN. METHODS AND RESULTS: SAP tissue was isolated from the rat and the leading pacemaker site was characterized. Cell size at the leading pacemaker site in the SAP was smaller than in the RA and comparable to that in the SAN. mRNA levels showed the SAP to be similar to, but distinct from, the SAN. For example, in the SAN and SAP, expression of Tbx3 and HCN1 was higher and Nav1.5 and Cx43 lower than in the RA. Organ-cultured SAP tissue beat spontaneously, but at a slower rate than the SAN. Adenovirus-mediated gene transfer of HCN2 and the chimeric protein HCN212 significantly increased the pacemaker rate of the SAP close to that of the native SAN, but HCN4 was ineffective. CONCLUSION: SAP tissue near the inferior vena cava is bradycardic, but shares characteristics with the SAN. Pacing can be accelerated by the over-expression of HCN2 or HCN212. This provides proof of concept for the use of SAP tissue as a substrate for biopacemaking in the treatment of SSS.
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Morris et al. (2013) studied Sick sinus syndrome (experimental model). Adenovirus-mediated gene transfer of HCN2 and HCN212 vs. Native sinoatrial node (SAN) or untreated SAP tissue was evaluated on Pacemaker rate. Adenovirus-mediated gene transfer of HCN2 and HCN212 significantly increased the pacemaker rate of rat subsidiary atrial pacemaker tissue close to that of the native sinoatrial node.
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