Functional roles of a Ca2+-activated K+ channel in atrioventricular nodes
Functional roles of a Ca2+-activated K+ channel in atrioventricular nodes
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Ca2 激活的 K 通道在房室结中的功能作用
DOI：
10.1161/circresaha.107.161778
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发表时间：
2008-02-29
影响因子：
20.1
通讯作者：
Chiamvimonvat, Nipavan
中科院分区：
文献类型：
--
作者：
Zhang, Qian;Timofeyev, Valeriy;Chiamvimonvat, Nipavan
自从解剖性房室结(AVNs)首次被描述以来，大量的研究已经对AVNs结构的异质性以及控制这一复杂的房室传导通路的一系列离子通道蛋白提供了见解。这些研究揭示了多个结节和结节样肌细胞的复杂组织，有助于房室结在健康和疾病中的独特电生理学。另一方面，关于特定离子通道对AVN功能的贡献的信息仍然不完整。我们认为，房室结特异性离子通道的识别可能为临床上最常见的心律失常之一房扑/房颤的房室结传导控制提供一个更直接、更合理的治疗靶点。在这项研究中，我们利用了两个小电导钙激活的K+通道亚型SK2通道的1过表达或零突变的基因改变的小鼠模型，并在这些实验模型中展示了AVN功能障碍的强大表型。SK2通道的过度表达导致AVN细胞自发动作电位缩短和放电频率增加。另一方面，消融SK2通道对房室结的自发动作电位有相反的影响。此外，我们还利用多种技术直接记录了SK2通道在小鼠AVN中的表达。这些新的见解可能为房性心律失常的房室结传导的改进提供新的药物靶点。
Since the first description of the anatomical atrioventricular nodes (AVNs), a large number of studies have provided insights into the heterogeneity of the structure as well as a repertoire of ion channel proteins that govern this complex conduction pathway between the atria and ventricles. These studies have revealed the intricate organization of multiple nodal and nodal-like myocytes contributing to the unique electrophysiology of the AVN in health and diseases. On the other hand, information regarding the contribution of specific ion channels to the function of the AVN remains incomplete. We reason that the identification of AVN-specific ion channels may provide a more direct and rational design of therapeutic target in the control of AVN conduction in atrial flutter/fibrillation, one of the most common arrhythmias seen clinically. In this study, we took advantage of 2 genetically altered mouse models with overexpression or null mutation of 1 of a small conductance Ca2+-activated K+ channel isoform, SK2 channel, and demonstrated robust phenotypes of AVN dysfunction in these experimental models. Overexpression of SK2 channels results in the shortening of the spontaneous action potentials of the AVN cells and an increase in the firing frequency. On the other hand, ablation of the SK2 channel results in the opposite effects on the spontaneous action potentials of the AVN. Furthermore, we directly documented the expression of SK2 channel in mouse AVN using multiple techniques. The new insights may have important implications in providing novel drug targets for the modification of AVN conduction in the treatment of atrial arrhythmias.