The sodium channel NaX (encoded by the SCN7A gene) was originally identified in the heart and skeletal muscle and is structurally similar to the other voltage‐gated sodium channels but does not appear to be voltage gated. Although NaX is expressed at high levels in cardiac and skeletal muscle, little information exists on the function of NaX in these tissues. Transcriptional profiling of ion channels in the heart in a subset of patients with Brugada syndrome revealed an inverse relationship between the expression of NaX and NaV1.5 suggesting that, in cardiac myocytes, the expression of these channels may be linked. We propose that NaX plays a role in excitation–contraction coupling based on our experimental observations. Here we show that in cardiac myocytes, NaX is expressed in a striated pattern on the sarcolemma in regions corresponding to the sarcomeric M‐line. Knocking down NaX expression decreased NaV1.5 mRNA and protein and reduced the inward sodium current (INa+) following cell depolarization. When the expression of NaV1.5 was knocked down, ~85% of the INa+ was reduced consistent with the observations that NaV1.5 is the main voltage‐gated sodium channel in cardiac muscle and that NaX likely does not directly participate in mediating the INa+ following depolarization. Silencing NaV1.5 expression led to significant upregulation of NaX mRNA. Similar to NaV1.5, NaX protein levels were rapidly downregulated when the intracellular [Ca2+] was increased either by CaCl2 or caffeine. These data suggest that a relationship exists between NaX and NaV1.5 and that NaX may play a role in excitation–contraction coupling.

中文翻译：

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钠通道 Na X : 兴奋收缩耦合的可能参与者

钠通道 NaX（由 SCN7A 基因编码）最初在心脏和骨骼肌中被发现，在结构上与其他电压门控钠通道相似，但似乎没有电压门控。尽管 NaX 在心肌和骨骼肌中以高水平表达，但关于 NaX 在这些组织中的功能的信息很少。一部分 Brugada 综合征患者心脏中离子通道的转录分析显示 NaX 和 NaV1.5 的表达之间呈负相关，表明在心肌细胞中，这些通道的表达可能相关。根据我们的实验观察，我们建议 NaX 在兴奋-收缩耦合中起作用。在这里我们表明，在心肌细胞中，NaX 在与肌节 M 线相对应的区域的肌膜上以条纹模式表达。敲低 NaX 表达会降低 NaV1.5 mRNA 和蛋白质，并降低细胞去极化后的内向钠电流 (INa+)。当 NaV1.5 的表达被抑制时，约 85% 的 INa+ 减少，这与 NaV1.5 是心肌中主要的电压门控钠通道并且 NaX 可能不直接参与介导 INa+ 的观察结果一致去极化后。沉默 NaV1.5 表达导致 NaX mRNA 的显着上调。与 NaV1.5 类似，当 CaCl2 或咖啡因增加细胞内 [Ca2+] 时，NaX 蛋白水平迅速下调。这些数据表明 NaX 和 NaV1 之间存在关系。