Polyunsaturated fatty acid analogues differentially affect cardiac NaV, CaV, and KV channels through unique mechanisms
The cardiac ventricular action potential depends on several voltage-gated ion channels, including NaV, CaV, and KV channels. Mutations in these channels can cause Long QT Syndrome (LQTS) which increases the risk for ventricular fibrillation and sudden cardiac death. Polyunsaturated fatty acids (PUFA...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/51453 |
| _version_ | 1818019851680088064 |
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| author | Briana M Bohannon Alicia de la Cruz Xiaoan Wu Jessica J Jowais Marta E Perez Derek M Dykxhoorn Sara I Liin H Peter Larsson |
| author_facet | Briana M Bohannon Alicia de la Cruz Xiaoan Wu Jessica J Jowais Marta E Perez Derek M Dykxhoorn Sara I Liin H Peter Larsson |
| author_sort | Briana M Bohannon |
| collection | DOAJ |
| description | The cardiac ventricular action potential depends on several voltage-gated ion channels, including NaV, CaV, and KV channels. Mutations in these channels can cause Long QT Syndrome (LQTS) which increases the risk for ventricular fibrillation and sudden cardiac death. Polyunsaturated fatty acids (PUFAs) have emerged as potential therapeutics for LQTS because they are modulators of voltage-gated ion channels. Here we demonstrate that PUFA analogues vary in their selectivity for human voltage-gated ion channels involved in the ventricular action potential. The effects of specific PUFA analogues range from selective for a specific ion channel to broadly modulating cardiac ion channels from all three families (NaV, CaV, and KV). In addition, a PUFA analogue selective for the cardiac IKs channel (Kv7.1/KCNE1) is effective in shortening the cardiac action potential in human-induced pluripotent stem cell-derived cardiomyocytes. Our data suggest that PUFA analogues could potentially be developed as therapeutics for LQTS and cardiac arrhythmia. |
| first_indexed | 2024-04-14T07:57:59Z |
| format | Article |
| id | doaj.art-e07a4e0605884ed9905949525bae0d17 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:57:59Z |
| publishDate | 2020-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e07a4e0605884ed9905949525bae0d172022-12-22T02:04:59ZengeLife Sciences Publications LtdeLife2050-084X2020-03-01910.7554/eLife.51453Polyunsaturated fatty acid analogues differentially affect cardiac NaV, CaV, and KV channels through unique mechanismsBriana M Bohannon0https://orcid.org/0000-0002-3720-1477Alicia de la Cruz1Xiaoan Wu2Jessica J Jowais3Marta E Perez4Derek M Dykxhoorn5Sara I Liin6https://orcid.org/0000-0001-8493-0114H Peter Larsson7https://orcid.org/0000-0002-1688-2525Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, United StatesDepartment of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, United StatesDepartment of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, United StatesDepartment of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, United StatesDepartment of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, United StatesJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, United StatesDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, SwedenDepartment of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, United StatesThe cardiac ventricular action potential depends on several voltage-gated ion channels, including NaV, CaV, and KV channels. Mutations in these channels can cause Long QT Syndrome (LQTS) which increases the risk for ventricular fibrillation and sudden cardiac death. Polyunsaturated fatty acids (PUFAs) have emerged as potential therapeutics for LQTS because they are modulators of voltage-gated ion channels. Here we demonstrate that PUFA analogues vary in their selectivity for human voltage-gated ion channels involved in the ventricular action potential. The effects of specific PUFA analogues range from selective for a specific ion channel to broadly modulating cardiac ion channels from all three families (NaV, CaV, and KV). In addition, a PUFA analogue selective for the cardiac IKs channel (Kv7.1/KCNE1) is effective in shortening the cardiac action potential in human-induced pluripotent stem cell-derived cardiomyocytes. Our data suggest that PUFA analogues could potentially be developed as therapeutics for LQTS and cardiac arrhythmia.https://elifesciences.org/articles/51453Xenopus oocytesiksCav1.2Nav1.5Long QT Syndromepolyunsaturated fatty acids |
| spellingShingle | Briana M Bohannon Alicia de la Cruz Xiaoan Wu Jessica J Jowais Marta E Perez Derek M Dykxhoorn Sara I Liin H Peter Larsson Polyunsaturated fatty acid analogues differentially affect cardiac NaV, CaV, and KV channels through unique mechanisms eLife Xenopus oocytes iks Cav1.2 Nav1.5 Long QT Syndrome polyunsaturated fatty acids |
| title | Polyunsaturated fatty acid analogues differentially affect cardiac NaV, CaV, and KV channels through unique mechanisms |
| title_full | Polyunsaturated fatty acid analogues differentially affect cardiac NaV, CaV, and KV channels through unique mechanisms |
| title_fullStr | Polyunsaturated fatty acid analogues differentially affect cardiac NaV, CaV, and KV channels through unique mechanisms |
| title_full_unstemmed | Polyunsaturated fatty acid analogues differentially affect cardiac NaV, CaV, and KV channels through unique mechanisms |
| title_short | Polyunsaturated fatty acid analogues differentially affect cardiac NaV, CaV, and KV channels through unique mechanisms |
| title_sort | polyunsaturated fatty acid analogues differentially affect cardiac nav cav and kv channels through unique mechanisms |
| topic | Xenopus oocytes iks Cav1.2 Nav1.5 Long QT Syndrome polyunsaturated fatty acids |
| url | https://elifesciences.org/articles/51453 |
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