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Title: The sodium channel Na X : Possible player in excitation–contraction coupling

Abstract

Abstract The sodium channel Na X (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 X is expressed at high levels in cardiac and skeletal muscle, little information exists on the function of Na X 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 X and Na V 1.5 suggesting that, in cardiac myocytes, the expression of these channels may be linked. We propose that Na X plays a role in excitation–contraction coupling based on our experimental observations. Here we show that in cardiac myocytes, Na X is expressed in a striated pattern on the sarcolemma in regions corresponding to the sarcomeric M‐line. Knocking down Na X expression decreased Na V 1.5 mRNA and protein and reduced the inward sodium current ( I Na+ ) following cell depolarization. When the expression of Na V 1.5 was knocked down, ~85% of the I Na+ was reduced consistent with the observations that Na V 1.5 is the mainmore » voltage‐gated sodium channel in cardiac muscle and that Na X likely does not directly participate in mediating the I Na+ following depolarization. Silencing Na V 1.5 expression led to significant upregulation of Na X mRNA. Similar to Na V 1.5, Na X protein levels were rapidly downregulated when the intracellular [Ca 2+ ] was increased either by CaCl 2 or caffeine. These data suggest that a relationship exists between Na X and Na V 1.5 and that Na X may play a role in excitation–contraction coupling.« less

Authors:
ORCiD logo [1];  [2];  [2];  [1];  [1];  [1];  [3];  [2];  [2];  [1]
  1. Department of Surgery Feinberg School of Medicine, Northwestern University Chicago Illinois
  2. Feinberg School of Medicine Northwestern University Chicago Illinois
  3. Department of Dental and Maxillofacial Trauma Institute of Surgical Research Texas
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1598062
Resource Type:
Publisher's Accepted Manuscript
Journal Name:
IUBMB Life
Additional Journal Information:
Journal Name: IUBMB Life Journal Volume: 72 Journal Issue: 4; Journal ID: ISSN 1521-6543
Publisher:
Wiley Blackwell (John Wiley & Sons)
Country of Publication:
France
Language:
English

Citation Formats

Bogdanovic, Elena, Potet, Franck, Marszalec, William, Iyer, Hari, Galiano, Robert, Hong, Seok J., Leung, Kai P., Wasserstrom, John Andrew, George, Jr., Alfred L., and Mustoe, Thomas A. The sodium channel Na X : Possible player in excitation–contraction coupling. France: N. p., 2020. Web. doi:10.1002/iub.2247.
Bogdanovic, Elena, Potet, Franck, Marszalec, William, Iyer, Hari, Galiano, Robert, Hong, Seok J., Leung, Kai P., Wasserstrom, John Andrew, George, Jr., Alfred L., & Mustoe, Thomas A. The sodium channel Na X : Possible player in excitation–contraction coupling. France. https://doi.org/10.1002/iub.2247
Bogdanovic, Elena, Potet, Franck, Marszalec, William, Iyer, Hari, Galiano, Robert, Hong, Seok J., Leung, Kai P., Wasserstrom, John Andrew, George, Jr., Alfred L., and Mustoe, Thomas A. Thu . "The sodium channel Na X : Possible player in excitation–contraction coupling". France. https://doi.org/10.1002/iub.2247.
@article{osti_1598062,
title = {The sodium channel Na X : Possible player in excitation–contraction coupling},
author = {Bogdanovic, Elena and Potet, Franck and Marszalec, William and Iyer, Hari and Galiano, Robert and Hong, Seok J. and Leung, Kai P. and Wasserstrom, John Andrew and George, Jr., Alfred L. and Mustoe, Thomas A.},
abstractNote = {Abstract The sodium channel Na X (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 X is expressed at high levels in cardiac and skeletal muscle, little information exists on the function of Na X 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 X and Na V 1.5 suggesting that, in cardiac myocytes, the expression of these channels may be linked. We propose that Na X plays a role in excitation–contraction coupling based on our experimental observations. Here we show that in cardiac myocytes, Na X is expressed in a striated pattern on the sarcolemma in regions corresponding to the sarcomeric M‐line. Knocking down Na X expression decreased Na V 1.5 mRNA and protein and reduced the inward sodium current ( I Na+ ) following cell depolarization. When the expression of Na V 1.5 was knocked down, ~85% of the I Na+ was reduced consistent with the observations that Na V 1.5 is the main voltage‐gated sodium channel in cardiac muscle and that Na X likely does not directly participate in mediating the I Na+ following depolarization. Silencing Na V 1.5 expression led to significant upregulation of Na X mRNA. Similar to Na V 1.5, Na X protein levels were rapidly downregulated when the intracellular [Ca 2+ ] was increased either by CaCl 2 or caffeine. These data suggest that a relationship exists between Na X and Na V 1.5 and that Na X may play a role in excitation–contraction coupling.},
doi = {10.1002/iub.2247},
journal = {IUBMB Life},
number = 4,
volume = 72,
place = {France},
year = {2020},
month = {2}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1002/iub.2247

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Cited by: 3 works
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