Methylmercury Poisoning Induces Cardiac Electrical Remodeling and Increases Arrhythmia Susceptibility and Mortality
This study aims to investigate the cardiac electrical remodeling associated with intoxication by methylmercury (MeHg). We evaluated the chronic effects of MeHg on in vivo electrocardiograms and on ex vivo action potentials and depolarizing (I<sub>Ca-L</sub>) and repolarizing (I<sub>...
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MDPI AG
2020-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/10/3490 |
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| author | Mara Cristina P. Santos Ruybal Monica Gallego Thais Bazoti B. Sottani Emiliano H. Medei Oscar Casis Jose Hamilton M. Nascimento |
| author_facet | Mara Cristina P. Santos Ruybal Monica Gallego Thais Bazoti B. Sottani Emiliano H. Medei Oscar Casis Jose Hamilton M. Nascimento |
| author_sort | Mara Cristina P. Santos Ruybal |
| collection | DOAJ |
| description | This study aims to investigate the cardiac electrical remodeling associated with intoxication by methylmercury (MeHg). We evaluated the chronic effects of MeHg on in vivo electrocardiograms and on ex vivo action potentials and depolarizing (I<sub>Ca-L</sub>) and repolarizing (I<sub>to</sub>) currents. The acute effect of MeHg was evaluated on HEK293 cells expressing human ERG, Kv4.3 and KCNQ1/KCNE1 channels. Chronic MeHg treatment increased QTc and T<sub>peak</sub>–T<sub>end</sub> interval duration, prolonged action potential duration and decreased amplitude of I<sub>to</sub> and I<sub>Ca-L</sub>. In addition, heterologously expressed I<sub>hKv4.3</sub>, I<sub>hERG</sub> or I<sub>hKCNQ1/KCNE1</sub> decreased after acute exposure to MeHg at subnanomolar range. The introduction of the in vitro effects of MeHg in a computer model of human ventricular action potentials triggered early afterdepolarizations and arrhythmia. In conclusion, cardiac electrical remodeling induced by MeHg poisoning is related to the reduction of I<sub>to</sub> and I<sub>Ca-L</sub>. The acute effect of MeHg on hKv4.3; hERG and hKCNQ1/KCNE1 currents and their transposition to in silico models show an association between MeHg intoxication and acquired Long QT Syndrome in humans. MeHg can exert its high toxicity either after chronic or acute exposure to concentrations as low as picomolar. |
| first_indexed | 2024-03-10T19:49:43Z |
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| language | English |
| last_indexed | 2024-03-10T19:49:43Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7d9c1da6c7444d79b4ba8790acb922772023-11-20T00:32:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-012110349010.3390/ijms21103490Methylmercury Poisoning Induces Cardiac Electrical Remodeling and Increases Arrhythmia Susceptibility and MortalityMara Cristina P. Santos Ruybal0Monica Gallego1Thais Bazoti B. Sottani2Emiliano H. Medei3Oscar Casis4Jose Hamilton M. Nascimento5Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, BrazilDepartamento de Fisiología, Facultad de Farmacia, Universidad del País Vasco UPV/EHU, 01006 Vitoria, SpainInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, BrazilDepartamento de Fisiología, Facultad de Farmacia, Universidad del País Vasco UPV/EHU, 01006 Vitoria, SpainInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, BrazilThis study aims to investigate the cardiac electrical remodeling associated with intoxication by methylmercury (MeHg). We evaluated the chronic effects of MeHg on in vivo electrocardiograms and on ex vivo action potentials and depolarizing (I<sub>Ca-L</sub>) and repolarizing (I<sub>to</sub>) currents. The acute effect of MeHg was evaluated on HEK293 cells expressing human ERG, Kv4.3 and KCNQ1/KCNE1 channels. Chronic MeHg treatment increased QTc and T<sub>peak</sub>–T<sub>end</sub> interval duration, prolonged action potential duration and decreased amplitude of I<sub>to</sub> and I<sub>Ca-L</sub>. In addition, heterologously expressed I<sub>hKv4.3</sub>, I<sub>hERG</sub> or I<sub>hKCNQ1/KCNE1</sub> decreased after acute exposure to MeHg at subnanomolar range. The introduction of the in vitro effects of MeHg in a computer model of human ventricular action potentials triggered early afterdepolarizations and arrhythmia. In conclusion, cardiac electrical remodeling induced by MeHg poisoning is related to the reduction of I<sub>to</sub> and I<sub>Ca-L</sub>. The acute effect of MeHg on hKv4.3; hERG and hKCNQ1/KCNE1 currents and their transposition to in silico models show an association between MeHg intoxication and acquired Long QT Syndrome in humans. MeHg can exert its high toxicity either after chronic or acute exposure to concentrations as low as picomolar.https://www.mdpi.com/1422-0067/21/10/3490mercurycardiacelectrical remodelingion currentarrhythmia |
| spellingShingle | Mara Cristina P. Santos Ruybal Monica Gallego Thais Bazoti B. Sottani Emiliano H. Medei Oscar Casis Jose Hamilton M. Nascimento Methylmercury Poisoning Induces Cardiac Electrical Remodeling and Increases Arrhythmia Susceptibility and Mortality International Journal of Molecular Sciences mercury cardiac electrical remodeling ion current arrhythmia |
| title | Methylmercury Poisoning Induces Cardiac Electrical Remodeling and Increases Arrhythmia Susceptibility and Mortality |
| title_full | Methylmercury Poisoning Induces Cardiac Electrical Remodeling and Increases Arrhythmia Susceptibility and Mortality |
| title_fullStr | Methylmercury Poisoning Induces Cardiac Electrical Remodeling and Increases Arrhythmia Susceptibility and Mortality |
| title_full_unstemmed | Methylmercury Poisoning Induces Cardiac Electrical Remodeling and Increases Arrhythmia Susceptibility and Mortality |
| title_short | Methylmercury Poisoning Induces Cardiac Electrical Remodeling and Increases Arrhythmia Susceptibility and Mortality |
| title_sort | methylmercury poisoning induces cardiac electrical remodeling and increases arrhythmia susceptibility and mortality |
| topic | mercury cardiac electrical remodeling ion current arrhythmia |
| url | https://www.mdpi.com/1422-0067/21/10/3490 |
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