Abstract 13052: Functional and Molecular Comparison of Subsidiary Right Atrial Pacemaker Tissue to the Sinoatrial Node
Subsidiary atrial pacemaker (SAP) tissue has been described in the right atrium (RA) above the inferior vena cava which may play a role in atrial arrhythmias. This study aims to elaborate on its functional and molecular character and compare it to the sinoatrial node (SAN).
SAN and SAP tissues were isolated in vitro from rat RA. Pacing rate was recorded under control conditions (Tyrode’s solution) and in the presence of ivabradine 3 μM, isoprenaline 0.05 μM or ryanodine 2 μM, and compared by t-test. 1 mm tissue biopsies were taken from the SAN, SAP and RA for RT-qPCR with data analysed by limma and hierarchical clustering (Pearson distances). mRNA levels in the SAP were similar to, but distinct from, the SAN. Of the 91 analysed, 23 differed between the three tissue types. In the SAN and SAP, expression of Tbx3 and HCN1 was higher and Nav1.5 and Cx43 lower than in the RA myocardium. Only the SAN expressed HCN4 more than the RA myocardium. It was not possible to fully separate the SAP from the SAN on hierarchical clustering. SAP pacing rate was slower than the SAN under control conditions (mean cycle lengths: 242±14 ms vs 202±6 ms; n=16; p≤0.05). Ivabradine decreased pacing rate in the SAP by 33±6 % (n=5; p≤0.05) and the SAN by 40±4 % (n=5; p≤0.001). Isoprenaline increased pacing rate in the SAP by 32±8 % (n=5; p≤0.01) and the SAN by 54±8 % (n=5; p≤0.001). Ryanodine reduced pacing rate in the SAP by 18±4 % (n=6; p≤0.01) and the SAN by 24±6 % (n=6; p≤0.05).
SAP tissue is phenotypically distinct from the SAN which may account for its slower pacing rate. HCN4 mRNA levels were lower in the SAP than the SAN however the response to If blockade was similar. It may be that SAP tissue pacing is dependent on HCN1 instead. We also found no difference between the SAP and SAN in response to β-adrenergic stimulation or Ca2+ clock inhibition suggesting these mechanisms contribute similarly to both tissues. These results may further our understanding of the pacemaker mechanisms of atrial arrhythmias and their response to drug therapy.
- © 2013 by American Heart Association, Inc.