A sodium channel therapeutic target
<p dir="ltr">Recent large-scale genomic studies have identified a sodium channel isoform that seems to be responsible for the heart’s ability to conduct electrical impulses. A new review by Thomas Zimmer of Friedrich Schiller University in Germany summarises the new findings, and how...
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2015
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| _version_ | 1864513559526899712 |
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| author | Nature Research (16552612) |
| author_facet | Nature Research (16552612) |
| author_role | author |
| dc.creator.none.fl_str_mv | Nature Research (16552612) |
| dc.date.none.fl_str_mv | 2015-02-28T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.57945/manara.23909685.v1 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/online_resource/A_sodium_channel_therapeutic_target/23909685 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Cardiovascular medicine and haematology cardiology sodium heart cells sodium channel isoform SCN10A SCN5A |
| dc.title.none.fl_str_mv | A sodium channel therapeutic target |
| dc.type.none.fl_str_mv | Text Online resource info:eu-repo/semantics/publishedVersion text |
| description | <p dir="ltr">Recent large-scale genomic studies have identified a sodium channel isoform that seems to be responsible for the heart’s ability to conduct electrical impulses. A new review by Thomas Zimmer of Friedrich Schiller University in Germany summarises the new findings, and how they may eventually lead to novel treatments for a variety of life-threatening heart conditions. Voltage-gated sodium channels are barrel-shaped proteins embedded in the membranes of electrically excitable cells, such as neurons and heart muscle. They control the cells’ electrical properties by regulating the inward flow of sodium ions through a central pore. Mammals express nine different sodium channel isoforms, which are made up of multiple subunits, and are largely characterized by their sensitivity to tetrodotoxin (TTX), which can block their function by plugging the pore. Three of these channels — Na 1.5, which is expressed in the heart, and Na 1.8 and Na 1.9, which are expressed by nerve cells — are relatively resistant to TTX, whereas the other six, expressed in skeletal muscle and the central and peripheral nervous systems, are highly sensitive to it. A number of recent genome-wide association studies have shown that the SCN10A gene, which encodes sodium channel Na 1.8, determines the conduction properties of heart cells, even though it is found in relatively low levels in the organ. Mutations in this gene are also associated with Brugada syndrome, a condition that causes heart beats irregularities. “The discovery of Na 1.8 as a relevant player in the heart is another important milestone towards the understanding of cardiac excitability,” says Zimmer. “The actual role [it plays] in the heart remains obscure [but] ongoing research may solve this issue.” Other studies show that Na 1.8 is expressed in neurons in the heart, suggesting that it regulates the electrical activity of these cells. It is also found in heart muscle cells, and SCN10A is now known to also regulate expression of Na 1.5, the most prominent sodium channel in the heart, by interacting with the SCN5A gene. These recent findings suggest that SCN10A/Na 1.8 may be a target that could potentially lead to novel treatments for Brugada syndrome and other related conditions. The next step is to understand how exactly SCN10A exerts its effect, explains Zimmer. “It is important to clarify whether the essential function of SCN10A occurs via regulating SCN5A expression or via the electrophysiological properties of the gene product Na 1.8, and to demonstrate in which cardiac cells of the human heart the channel is expressed,”he adds.</p><p><br></p><h2>Other Information</h2><p dir="ltr">Published in: QScience.com Highlights, Published by Nature Research for Hamad bin Khalifa University Press (HBKU Press)<br>License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_a6ee208bd50491d4e4a32ff72cc0408d |
| identifier_str_mv | 10.57945/manara.23909685.v1 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/23909685 |
| publishDate | 2015 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | A sodium channel therapeutic targetNature Research (16552612)Biomedical and clinical sciencesCardiovascular medicine and haematologycardiologysodiumheart cellssodium channel isoformSCN10ASCN5A<p dir="ltr">Recent large-scale genomic studies have identified a sodium channel isoform that seems to be responsible for the heart’s ability to conduct electrical impulses. A new review by Thomas Zimmer of Friedrich Schiller University in Germany summarises the new findings, and how they may eventually lead to novel treatments for a variety of life-threatening heart conditions. Voltage-gated sodium channels are barrel-shaped proteins embedded in the membranes of electrically excitable cells, such as neurons and heart muscle. They control the cells’ electrical properties by regulating the inward flow of sodium ions through a central pore. Mammals express nine different sodium channel isoforms, which are made up of multiple subunits, and are largely characterized by their sensitivity to tetrodotoxin (TTX), which can block their function by plugging the pore. Three of these channels — Na 1.5, which is expressed in the heart, and Na 1.8 and Na 1.9, which are expressed by nerve cells — are relatively resistant to TTX, whereas the other six, expressed in skeletal muscle and the central and peripheral nervous systems, are highly sensitive to it. A number of recent genome-wide association studies have shown that the SCN10A gene, which encodes sodium channel Na 1.8, determines the conduction properties of heart cells, even though it is found in relatively low levels in the organ. Mutations in this gene are also associated with Brugada syndrome, a condition that causes heart beats irregularities. “The discovery of Na 1.8 as a relevant player in the heart is another important milestone towards the understanding of cardiac excitability,” says Zimmer. “The actual role [it plays] in the heart remains obscure [but] ongoing research may solve this issue.” Other studies show that Na 1.8 is expressed in neurons in the heart, suggesting that it regulates the electrical activity of these cells. It is also found in heart muscle cells, and SCN10A is now known to also regulate expression of Na 1.5, the most prominent sodium channel in the heart, by interacting with the SCN5A gene. These recent findings suggest that SCN10A/Na 1.8 may be a target that could potentially lead to novel treatments for Brugada syndrome and other related conditions. The next step is to understand how exactly SCN10A exerts its effect, explains Zimmer. “It is important to clarify whether the essential function of SCN10A occurs via regulating SCN5A expression or via the electrophysiological properties of the gene product Na 1.8, and to demonstrate in which cardiac cells of the human heart the channel is expressed,”he adds.</p><p><br></p><h2>Other Information</h2><p dir="ltr">Published in: QScience.com Highlights, Published by Nature Research for Hamad bin Khalifa University Press (HBKU Press)<br>License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br></p>2015-02-28T00:00:00ZTextOnline resourceinfo:eu-repo/semantics/publishedVersiontext10.57945/manara.23909685.v1https://figshare.com/articles/online_resource/A_sodium_channel_therapeutic_target/23909685CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/239096852015-02-28T00:00:00Z |
| spellingShingle | A sodium channel therapeutic target Nature Research (16552612) Biomedical and clinical sciences Cardiovascular medicine and haematology cardiology sodium heart cells sodium channel isoform SCN10A SCN5A |
| status_str | publishedVersion |
| title | A sodium channel therapeutic target |
| title_full | A sodium channel therapeutic target |
| title_fullStr | A sodium channel therapeutic target |
| title_full_unstemmed | A sodium channel therapeutic target |
| title_short | A sodium channel therapeutic target |
| title_sort | A sodium channel therapeutic target |
| topic | Biomedical and clinical sciences Cardiovascular medicine and haematology cardiology sodium heart cells sodium channel isoform SCN10A SCN5A |