Characterization of a right atrial subsidiary pacemaker and acceleration of the pacing rate by HCN over-expression
Characterization of a right atrial subsidiary pacemaker and acceleration of the pacing rate by HCN over-expression
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DOI：
10.1093/cvr/cvt164
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发表时间：
2013-10-01
影响因子：
10.8
通讯作者：
Boyett, Mark R.
中科院分区：
文献类型：
--
作者：
Morris, Gwilym M.;D'Souza, Alicia;Boyett, Mark R.
尽管右心房 (RA) 包含附属心房起搏器 (SAP) 组织，在病态窦房结综合征 (SSS) 中可以取代窦房结 (SAN)，但 SAP 组织是心动过缓的。我们对 SAP 组织知之甚少，该研究的一个目的是表征离子通道表达，以深入了解 SAP 起搏器机制。第二个目的是确定 HCN 过度表达（一种类似生物起搏器的策略）是否可以加速起搏器速率，从而产生本质上与右心房起搏器相似的起搏器。从大鼠中分离出 SAN.SAP 组织，并表征了 SAP 中主导起搏器部位的细胞大小，并且与 SAN 中的细胞大小相当，表明 SAP 与 SAN 中相似，但又不同。例如，在 SAN 和 SAP 中，Tbx3 和 HCN1 的表达高于 RA，而 Nav1.5 和 Cx43 的表达低于 RA。 HCN2 和嵌合蛋白 HCN212 的腺病毒介导的基因转移显着提高了 SAP 的起搏率，接近于天然 SAN，但 HCN4 无效。下腔静脉附近的 SAP 组织心动过缓，但与 SAN 具有相同的特征。这为使用 SAP 组织作为生物起搏基质提供了概念证明。在 SSS 的治疗中。
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.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.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.