The sodium channel Na : Possible player in excitation-contraction coupling.

The sodium channel Na (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 Na is expressed at high levels in cardiac and skeletal muscle, little information exists on the function of Na 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 Na and Na 1.5 suggesting that, in cardiac myocytes, the expression of these channels may be linked. We propose that Na plays a role in excitation-contraction coupling based on our experimental observations. Here we show that in cardiac myocytes, Na is expressed in a striated pattern on the sarcolemma in regions corresponding to the sarcomeric M-line. Knocking down Na expression decreased Na 1.5 mRNA and protein and reduced the inward sodium current (I ) following cell depolarization. When the expression of Na 1.5 was knocked down, ~85% of the I was reduced consistent with the observations that Na 1.5 is the main voltage-gated sodium channel in cardiac muscle and that Na likely does not directly participate in mediating the I following depolarization. Silencing Na 1.5 expression led to significant upregulation of Na mRNA. Similar to Na 1.5, Na protein levels were rapidly downregulated when the intracellular [Ca ] was increased either by CaCl or caffeine. These data suggest that a relationship exists between Na and Na 1.5 and that Na may play a role in excitation-contraction coupling.