Neuronal Nav1.8 Channels as a Novel Therapeutic Target of Acute Atrial Fibrillation Prevention
BackgroundGanglionated plexus have been developed as additional ablation targets to improve the outcome of atrial fibrillation (AF) besides pulmonary vein isolation. Recent studies implicated an intimate relationship between neuronal sodium channel Nav1.8 (encoded by SCN10A) and AF. The underlying m...
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| Format: | Article |
| Language: | English |
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Wiley
2016-10-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.116.004050 |
| _version_ | 1811334032157310976 |
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| author | XiaoMeng Chen LiLei Yu ShaoBo Shi Hong Jiang CongXin Huang Mayurika Desai YiGang Li Hector Barajas‐Martinez Dan Hu |
| author_facet | XiaoMeng Chen LiLei Yu ShaoBo Shi Hong Jiang CongXin Huang Mayurika Desai YiGang Li Hector Barajas‐Martinez Dan Hu |
| author_sort | XiaoMeng Chen |
| collection | DOAJ |
| description | BackgroundGanglionated plexus have been developed as additional ablation targets to improve the outcome of atrial fibrillation (AF) besides pulmonary vein isolation. Recent studies implicated an intimate relationship between neuronal sodium channel Nav1.8 (encoded by SCN10A) and AF. The underlying mechanism between Nav1.8 and AF remains unclear. This study aimed to determine the role of Nav1.8 in cardiac electrophysiology in an acute AF model and explore possible therapeutic targets. Methods and ResultsImmunohistochemical study was used on canine cardiac ganglionated plexus. Both Nav1.5 and Nav1.8 were expressed in ganglionated plexus with canonical neuronal markers. Sixteen canines were randomly administered either saline or the Nav1.8 blocker A‐803467. Electrophysiological study was compared between the 2 groups before and after 6‐hour rapid atrial pacing. Compared with the control group, administration of A‐803467 decreased the incidence of AF (87.5% versus 25.0%, P<0.05), shortened AF duration, and prolonged AF cycle length. A‐803467 also significantly suppressed the decrease in the effective refractory period and the increase in effective refractory period dispersion and cumulative window of vulnerability caused by rapid atrial pacing in all recording sites. Patch clamp study was performed under 100 nmol/L A‐803467 in TSA201 cells cotransfected with SCN10A‐WT, SCN5A‐WT, and SCN3B‐WT. INa,P was reduced by 45.34% at −35 mV, and INa,L by 68.57% at −20 mV. Evident fast inactivation, slow recovery, and use‐dependent block were also discovered after applying the drug. ConclusionsOur study demonstrates that Nav1.8 could exert its effect on electrophysiological characteristics through cardiac ganglionated plexus. It indicates that Nav1.8 is a novel target in understanding cardiac electrophysiology and SCN10A‐related arrhythmias. |
| first_indexed | 2024-04-13T17:01:43Z |
| format | Article |
| id | doaj.art-c08b7305a5d74dedb29973958a9dd76b |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-13T17:01:43Z |
| publishDate | 2016-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-c08b7305a5d74dedb29973958a9dd76b2022-12-22T02:38:38ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802016-10-0151110.1161/JAHA.116.004050Neuronal Nav1.8 Channels as a Novel Therapeutic Target of Acute Atrial Fibrillation PreventionXiaoMeng Chen0LiLei Yu1ShaoBo Shi2Hong Jiang3CongXin Huang4Mayurika Desai5YiGang Li6Hector Barajas‐Martinez7Dan Hu8Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Cardiology and Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology and Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology and Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology and Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan, ChinaMasonic Medical Research Laboratory, Utica, NYDepartment of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaMasonic Medical Research Laboratory, Utica, NYDepartment of Cardiology and Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan, ChinaBackgroundGanglionated plexus have been developed as additional ablation targets to improve the outcome of atrial fibrillation (AF) besides pulmonary vein isolation. Recent studies implicated an intimate relationship between neuronal sodium channel Nav1.8 (encoded by SCN10A) and AF. The underlying mechanism between Nav1.8 and AF remains unclear. This study aimed to determine the role of Nav1.8 in cardiac electrophysiology in an acute AF model and explore possible therapeutic targets. Methods and ResultsImmunohistochemical study was used on canine cardiac ganglionated plexus. Both Nav1.5 and Nav1.8 were expressed in ganglionated plexus with canonical neuronal markers. Sixteen canines were randomly administered either saline or the Nav1.8 blocker A‐803467. Electrophysiological study was compared between the 2 groups before and after 6‐hour rapid atrial pacing. Compared with the control group, administration of A‐803467 decreased the incidence of AF (87.5% versus 25.0%, P<0.05), shortened AF duration, and prolonged AF cycle length. A‐803467 also significantly suppressed the decrease in the effective refractory period and the increase in effective refractory period dispersion and cumulative window of vulnerability caused by rapid atrial pacing in all recording sites. Patch clamp study was performed under 100 nmol/L A‐803467 in TSA201 cells cotransfected with SCN10A‐WT, SCN5A‐WT, and SCN3B‐WT. INa,P was reduced by 45.34% at −35 mV, and INa,L by 68.57% at −20 mV. Evident fast inactivation, slow recovery, and use‐dependent block were also discovered after applying the drug. ConclusionsOur study demonstrates that Nav1.8 could exert its effect on electrophysiological characteristics through cardiac ganglionated plexus. It indicates that Nav1.8 is a novel target in understanding cardiac electrophysiology and SCN10A‐related arrhythmias.https://www.ahajournals.org/doi/10.1161/JAHA.116.004050atrial fibrillationelectrophysiologyganglionated plexusNav1.8SCN10A |
| spellingShingle | XiaoMeng Chen LiLei Yu ShaoBo Shi Hong Jiang CongXin Huang Mayurika Desai YiGang Li Hector Barajas‐Martinez Dan Hu Neuronal Nav1.8 Channels as a Novel Therapeutic Target of Acute Atrial Fibrillation Prevention Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease atrial fibrillation electrophysiology ganglionated plexus Nav1.8 SCN10A |
| title | Neuronal Nav1.8 Channels as a Novel Therapeutic Target of Acute Atrial Fibrillation Prevention |
| title_full | Neuronal Nav1.8 Channels as a Novel Therapeutic Target of Acute Atrial Fibrillation Prevention |
| title_fullStr | Neuronal Nav1.8 Channels as a Novel Therapeutic Target of Acute Atrial Fibrillation Prevention |
| title_full_unstemmed | Neuronal Nav1.8 Channels as a Novel Therapeutic Target of Acute Atrial Fibrillation Prevention |
| title_short | Neuronal Nav1.8 Channels as a Novel Therapeutic Target of Acute Atrial Fibrillation Prevention |
| title_sort | neuronal nav1 8 channels as a novel therapeutic target of acute atrial fibrillation prevention |
| topic | atrial fibrillation electrophysiology ganglionated plexus Nav1.8 SCN10A |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.116.004050 |
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