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A Non-inactivating High-voltage-activated Two-Pore Na(+) Channel that Supports Ultra-long Action Potentials and Membrane Bistability
Action potentials (APs) are fundamental cellular electrical signals. The genesis of short APs lasting milliseconds is well understood. Ultra-long APs (ulAPs) lasting seconds to minutes also occur in eukaryotic organisms, but their biological functions and mechanisms of generation are largely unknown...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224019/ https://www.ncbi.nlm.nih.gov/pubmed/25256615 http://dx.doi.org/10.1038/ncomms6015 |
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author | Cang, Chunlei Aranda, Kimberly Ren, Dejian |
author_facet | Cang, Chunlei Aranda, Kimberly Ren, Dejian |
author_sort | Cang, Chunlei |
collection | PubMed |
description | Action potentials (APs) are fundamental cellular electrical signals. The genesis of short APs lasting milliseconds is well understood. Ultra-long APs (ulAPs) lasting seconds to minutes also occur in eukaryotic organisms, but their biological functions and mechanisms of generation are largely unknown. Here, we identify TPC3, a previously uncharacterized member of the two-pore channel protein family, as a new voltage-gated Na(+) channel (Na(V)) that generates ulAPs, and that establishes membrane potential bistability. Unlike the rapidly inactivating Na(V)s that generate short APs in neurons, TPC3 has a high activation threshold, activates slowly, and does not inactivate—three properties that help generate long-lasting APs and guard the membrane against unintended perturbation. In amphibian oocytes, TPC3 forms a channel similar to channels induced by depolarization and sperm entry into eggs. TPC3 homologs are present in plants and animals, and they may be important for cellular processes and behaviors associated with prolonged membrane depolarization. |
format | Online Article Text |
id | pubmed-4224019 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-42240192015-03-26 A Non-inactivating High-voltage-activated Two-Pore Na(+) Channel that Supports Ultra-long Action Potentials and Membrane Bistability Cang, Chunlei Aranda, Kimberly Ren, Dejian Nat Commun Article Action potentials (APs) are fundamental cellular electrical signals. The genesis of short APs lasting milliseconds is well understood. Ultra-long APs (ulAPs) lasting seconds to minutes also occur in eukaryotic organisms, but their biological functions and mechanisms of generation are largely unknown. Here, we identify TPC3, a previously uncharacterized member of the two-pore channel protein family, as a new voltage-gated Na(+) channel (Na(V)) that generates ulAPs, and that establishes membrane potential bistability. Unlike the rapidly inactivating Na(V)s that generate short APs in neurons, TPC3 has a high activation threshold, activates slowly, and does not inactivate—three properties that help generate long-lasting APs and guard the membrane against unintended perturbation. In amphibian oocytes, TPC3 forms a channel similar to channels induced by depolarization and sperm entry into eggs. TPC3 homologs are present in plants and animals, and they may be important for cellular processes and behaviors associated with prolonged membrane depolarization. 2014-09-26 /pmc/articles/PMC4224019/ /pubmed/25256615 http://dx.doi.org/10.1038/ncomms6015 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Cang, Chunlei Aranda, Kimberly Ren, Dejian A Non-inactivating High-voltage-activated Two-Pore Na(+) Channel that Supports Ultra-long Action Potentials and Membrane Bistability |
title | A Non-inactivating High-voltage-activated Two-Pore Na(+) Channel that Supports Ultra-long Action Potentials and Membrane Bistability |
title_full | A Non-inactivating High-voltage-activated Two-Pore Na(+) Channel that Supports Ultra-long Action Potentials and Membrane Bistability |
title_fullStr | A Non-inactivating High-voltage-activated Two-Pore Na(+) Channel that Supports Ultra-long Action Potentials and Membrane Bistability |
title_full_unstemmed | A Non-inactivating High-voltage-activated Two-Pore Na(+) Channel that Supports Ultra-long Action Potentials and Membrane Bistability |
title_short | A Non-inactivating High-voltage-activated Two-Pore Na(+) Channel that Supports Ultra-long Action Potentials and Membrane Bistability |
title_sort | non-inactivating high-voltage-activated two-pore na(+) channel that supports ultra-long action potentials and membrane bistability |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224019/ https://www.ncbi.nlm.nih.gov/pubmed/25256615 http://dx.doi.org/10.1038/ncomms6015 |
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