期刊
CIRCULATION RESEARCH
卷 91, 期 12, 页码 1176-1182出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.RES.0000046237.54156.0A
关键词
action potential conduction; sodium current; gap junctions; intercalated disks; slow conduction
资金
- NHLBI NIH HHS [R37-HL33343, R01 HL049054, R37 HL033343, R01-HL49054] Funding Source: Medline
It is well known that the sodium current (I-Na) and the degree of gap junctional electrical coupling are the key determinants of action potential (AP) conduction in cardiac tissue. Immunohistochemical studies have shown that sodium channels (NaChs) are preferentially located in intercalated disks (IDs). Using dual immunocytochemical staining, we confirmed the colocalization of NaChs with connexin43 in cultures of neonatal rat ventricular myocytes. In mathematical simulations of conduction using the Luo-Rudy dynamic model of the ventricular AP, we assessed the hypothesis that conduction could be modulated by the preferential localization of NaChs in IDs. Localization of I-Na at the ID caused a large negative potential in the intercellular cleft, which influenced conduction in two opposing ways, depending on the degree of electrical coupling: (1) for normal and moderately reduced coupling, the negative cleft potential led to a large overshoot of the transmembrane potential resulting in a decreased driving force for I-Na itself (self-attenuation), which slowed conduction; (2) for greatly reduced coupling (<10%), the negative cleft potential induced by I-Na in the prejunctional membrane led to suprathreshold depolarization of the postjunctional membrane, which facilitated and accelerated conduction. When cleft potential effects were not incorporated, conduction was not significantly affected by the ID localization of I-Na. By enhancing conduction through the establishment of cleft potentials, the localization of NaChs in IDs might protect the myocardium from conduction block, very slow conduction, and microreentry under conditions of greatly reduced coupling. Conversely, by supporting moderately slow conduction, this mechanism could also promote arrhythmias.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据