Simon A M, Goodenough D A, Paul D L
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Curr Biol. 1998 Feb 26;8(5):295-8. doi: 10.1016/s0960-9822(98)70113-7.
Activation of cardiac muscle is mediated by the His-Purkinje system, a discrete pathway containing fast-conducting cells (Purkinje fibers) which coordinate the spread of excitation from the atrioventricular node (AV node) to ventricular myocardium [1]. Although pathologies of this specialized conduction system are common in humans, especially among the elderly [2], their molecular bases have not been defined. Gap junctions are present at appositions between Purkinje fibers and could provide a mechanism for propagating impulses between these cells [3]. Studies of the expression of connexins - the family of proteins from which gap junctions are formed - reveal that connexin40 (Cx40) is prominent in the conduction system [4]. In order to study the role of gap junction communication in cardiac conduction, we generated mice that lack Cx40. Using electrocardiographic analysis, we show that Cx40 null mice have cardiac conduction abnormalities characteristic of first-degree atrioventricular block with associated bundle branch block. Thus, gap junctions are essential for the rapid conduction of impulses in the His-Purkinje system.
心肌的激活由希氏-浦肯野系统介导，这是一条离散的通路，包含快速传导细胞（浦肯野纤维），可协调兴奋从房室结（AV结）向心室肌的传播[1]。尽管这种特殊传导系统的病变在人类中很常见，尤其是在老年人中[2]，但其分子基础尚未明确。间隙连接存在于浦肯野纤维之间的连接处，可为这些细胞之间的冲动传播提供一种机制[3]。对连接蛋白（形成间隙连接的蛋白质家族）表达的研究表明，连接蛋白40（Cx40）在传导系统中很突出[4]。为了研究间隙连接通讯在心脏传导中的作用，我们培育了缺乏Cx40的小鼠。通过心电图分析，我们发现Cx40基因敲除小鼠具有一度房室传导阻滞伴相关束支阻滞的心脏传导异常特征。因此，间隙连接对于希氏-浦肯野系统中冲动的快速传导至关重要。
