Cohen S A
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA.
Circulation. 1996 Dec 15;94(12):3083-6. doi: 10.1161/01.cir.94.12.3083.
Of the five sodium channel subtypes expressed in cardiac tissues, the rat (rH1) and human (hH1) isoforms are thought to be the predominant subtypes on the basis of heterologous expression studies. In this study, subtype-specific antibodies and immunocytochemistry were used to confirm protein expression and to localize rH1 protein in cardiac tissues.
Subtype-specific antibodies immunolabeled adult rat heart tissue in a manner identical to that obtained with subtype-nonselective antibodies. All antibodies specifically bound to the surface and t-tubular systems of atrial and ventricular muscle cells. Cytoplasmic labeling, reflecting nascent sodium channels or cytoplasmic stores of sodium channel protein, was apparent. Most notably, all antibodies also specifically labeled the subset of intercalated disks located at the ends but not the sides of adjacent ventricular muscle cells.
rH1 is the predominant subtype expressed on rat atrial and ventricular muscle cells. rH1 protein localization in surface and t-tubular membranes is consistent with its proposed role in coordinating membrane depolarization along the length and deep within cardiac muscle cells. rH1 protein localization in terminal intercalated disks suggests that sodium channels may also act as a localized voltage-dependent current amplifier, raising the safety margin for conduction; they also may contribute to anisotropic or saltatory conduction in cardiac tissues. These electrophysiological properties would be particularly important under conditions of altered, channel function resulting from ion channel gene defects (e.g., long QT syndrome), antiarrhythmic drug therapy, ischemia, or other heart diseases by influencing the electrophysiological substrate for ventricular tachyarrhythmias.
在心脏组织中表达的五种钠通道亚型中，基于异源表达研究，大鼠（rH1）和人类（hH1）亚型被认为是主要亚型。在本研究中，使用亚型特异性抗体和免疫细胞化学来确认蛋白质表达并在心脏组织中定位rH1蛋白。
亚型特异性抗体以与亚型非选择性抗体相同的方式对成年大鼠心脏组织进行免疫标记。所有抗体均特异性结合心房和心室肌细胞的表面和横管系统。反映新生钠通道或钠通道蛋白胞质储存的胞质标记很明显。最值得注意的是，所有抗体还特异性标记了位于相邻心室肌细胞末端而非侧面的闰盘子集。
rH1是在大鼠心房和心室肌细胞上表达的主要亚型。rH1蛋白在表面和横管膜中的定位与其在协调心肌细胞长度和深度内的膜去极化中所提出的作用一致。rH1蛋白在终末闰盘中的定位表明钠通道也可能作为局部电压依赖性电流放大器，提高传导的安全边际；它们也可能有助于心脏组织中的各向异性或跳跃传导。在离子通道基因缺陷（例如长QT综合征）、抗心律失常药物治疗、缺血或其他心脏病导致通道功能改变的情况下，这些电生理特性通过影响室性快速心律失常的电生理底物可能尤为重要。
