Allitridi inhibits multiple cardiac potassium channels expressed in HEK 293 cells.
Allitridi (diallyl trisulfide) is an active compound (volatile oil) from garlic. The previous studies reported that allitridi had anti-arrhythmic effect. The potential ionic mechanisms are, however, not understood. The present study was designed to determine the effects of allitridi on cardiac potas...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3522701?pdf=render |
| _version_ | 1818175945761095680 |
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| author | Xiao-Hui Xu Hai-Ying Sun Yan-Hui Zhang Wei Wu Kui-Hao Chen Yi Liu Chun-Yu Deng Xi-Yong Yu Man-Wen Jin Gui-Rong Li |
| author_facet | Xiao-Hui Xu Hai-Ying Sun Yan-Hui Zhang Wei Wu Kui-Hao Chen Yi Liu Chun-Yu Deng Xi-Yong Yu Man-Wen Jin Gui-Rong Li |
| author_sort | Xiao-Hui Xu |
| collection | DOAJ |
| description | Allitridi (diallyl trisulfide) is an active compound (volatile oil) from garlic. The previous studies reported that allitridi had anti-arrhythmic effect. The potential ionic mechanisms are, however, not understood. The present study was designed to determine the effects of allitridi on cardiac potassium channels expressed in HEK 293 cells using a whole-cell patch voltage-clamp technique and mutagenesis. It was found that allitridi inhibited hKv4.3 channels (IC(50) = 11.4 µM) by binding to the open channel, shifting availability potential to hyperpolarization, and accelerating closed-state inactivation of the channel. The hKv4.3 mutants T366A, T367A, V392A, and I395A showed a reduced response to allitridi with IC(50)s of 35.5 µM, 44.7 µM, 23.7 µM, and 42.4 µM. In addition, allitridi decreased hKv1.5, hERG, hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells with IC(50)s of 40.2 µM, 19.6 µM and 17.7 µM. However, it slightly inhibited hKir2.1 current (100 µM, inhibited by 9.8% at -120 mV). Our results demonstrate for the first time that allitridi preferably blocks hKv4.3 current by binding to the open channel at T366 and T367 of P-loop helix, and at V392 and I395 of S6 domain. It has a weak inhibition of hKv1.5, hERG, and hKCNQ1/hKCNE1 currents. These effects may account for its anti-arrhythmic effect observed in experimental animal models. |
| first_indexed | 2024-12-11T20:08:22Z |
| format | Article |
| id | doaj.art-94ec8f6e397949cebf22472c9268831f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T20:08:22Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-94ec8f6e397949cebf22472c9268831f2022-12-22T00:52:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5155010.1371/journal.pone.0051550Allitridi inhibits multiple cardiac potassium channels expressed in HEK 293 cells.Xiao-Hui XuHai-Ying SunYan-Hui ZhangWei WuKui-Hao ChenYi LiuChun-Yu DengXi-Yong YuMan-Wen JinGui-Rong LiAllitridi (diallyl trisulfide) is an active compound (volatile oil) from garlic. The previous studies reported that allitridi had anti-arrhythmic effect. The potential ionic mechanisms are, however, not understood. The present study was designed to determine the effects of allitridi on cardiac potassium channels expressed in HEK 293 cells using a whole-cell patch voltage-clamp technique and mutagenesis. It was found that allitridi inhibited hKv4.3 channels (IC(50) = 11.4 µM) by binding to the open channel, shifting availability potential to hyperpolarization, and accelerating closed-state inactivation of the channel. The hKv4.3 mutants T366A, T367A, V392A, and I395A showed a reduced response to allitridi with IC(50)s of 35.5 µM, 44.7 µM, 23.7 µM, and 42.4 µM. In addition, allitridi decreased hKv1.5, hERG, hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells with IC(50)s of 40.2 µM, 19.6 µM and 17.7 µM. However, it slightly inhibited hKir2.1 current (100 µM, inhibited by 9.8% at -120 mV). Our results demonstrate for the first time that allitridi preferably blocks hKv4.3 current by binding to the open channel at T366 and T367 of P-loop helix, and at V392 and I395 of S6 domain. It has a weak inhibition of hKv1.5, hERG, and hKCNQ1/hKCNE1 currents. These effects may account for its anti-arrhythmic effect observed in experimental animal models.http://europepmc.org/articles/PMC3522701?pdf=render |
| spellingShingle | Xiao-Hui Xu Hai-Ying Sun Yan-Hui Zhang Wei Wu Kui-Hao Chen Yi Liu Chun-Yu Deng Xi-Yong Yu Man-Wen Jin Gui-Rong Li Allitridi inhibits multiple cardiac potassium channels expressed in HEK 293 cells. PLoS ONE |
| title | Allitridi inhibits multiple cardiac potassium channels expressed in HEK 293 cells. |
| title_full | Allitridi inhibits multiple cardiac potassium channels expressed in HEK 293 cells. |
| title_fullStr | Allitridi inhibits multiple cardiac potassium channels expressed in HEK 293 cells. |
| title_full_unstemmed | Allitridi inhibits multiple cardiac potassium channels expressed in HEK 293 cells. |
| title_short | Allitridi inhibits multiple cardiac potassium channels expressed in HEK 293 cells. |
| title_sort | allitridi inhibits multiple cardiac potassium channels expressed in hek 293 cells |
| url | http://europepmc.org/articles/PMC3522701?pdf=render |
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