Amiodarone inhibits apamin-sensitive potassium currents.
Apamin sensitive potassium current (I KAS), carried by the type 2 small conductance Ca(2+)-activated potassium (SK2) channels, plays an important role in post-shock action potential duration (APD) shortening and recurrent spontaneous ventricular fibrillation (VF) in failing ventricles.To test the hy...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3726612?pdf=render |
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| author | Isik Turker Chih-Chieh Yu Po-Cheng Chang Zhenhui Chen Yoshiro Sohma Shien-Fong Lin Peng-Sheng Chen Tomohiko Ai |
| author_facet | Isik Turker Chih-Chieh Yu Po-Cheng Chang Zhenhui Chen Yoshiro Sohma Shien-Fong Lin Peng-Sheng Chen Tomohiko Ai |
| author_sort | Isik Turker |
| collection | DOAJ |
| description | Apamin sensitive potassium current (I KAS), carried by the type 2 small conductance Ca(2+)-activated potassium (SK2) channels, plays an important role in post-shock action potential duration (APD) shortening and recurrent spontaneous ventricular fibrillation (VF) in failing ventricles.To test the hypothesis that amiodarone inhibits I KAS in human embryonic kidney 293 (HEK-293) cells.We used the patch-clamp technique to study I KAS in HEK-293 cells transiently expressing human SK2 before and after amiodarone administration.Amiodarone inhibited IKAS in a dose-dependent manner (IC50, 2.67 ± 0.25 µM with 1 µM intrapipette Ca(2+)). Maximal inhibition was observed with 50 µM amiodarone which inhibited 85.6 ± 3.1% of IKAS induced with 1 µM intrapipette Ca(2+) (n = 3). IKAS inhibition by amiodarone was not voltage-dependent, but was Ca(2+)-dependent: 30 µM amiodarone inhibited 81.5±1.9% of I KAS induced with 1 µM Ca(2+) (n = 4), and 16.4±4.9% with 250 nM Ca(2+) (n = 5). Desethylamiodarone, a major metabolite of amiodarone, also exerts voltage-independent but Ca(2+) dependent inhibition of I KAS.Both amiodarone and desethylamiodarone inhibit I KAS at therapeutic concentrations. The inhibition is independent of time and voltage, but is dependent on the intracellular Ca(2+) concentration. SK2 current inhibition may in part underlie amiodarone's effects in preventing electrical storm in failing ventricles. |
| first_indexed | 2024-12-10T14:59:15Z |
| format | Article |
| id | doaj.art-29c32367984b478c96ca52a2dde98311 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T14:59:15Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-29c32367984b478c96ca52a2dde983112022-12-22T01:44:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e7045010.1371/journal.pone.0070450Amiodarone inhibits apamin-sensitive potassium currents.Isik TurkerChih-Chieh YuPo-Cheng ChangZhenhui ChenYoshiro SohmaShien-Fong LinPeng-Sheng ChenTomohiko AiApamin sensitive potassium current (I KAS), carried by the type 2 small conductance Ca(2+)-activated potassium (SK2) channels, plays an important role in post-shock action potential duration (APD) shortening and recurrent spontaneous ventricular fibrillation (VF) in failing ventricles.To test the hypothesis that amiodarone inhibits I KAS in human embryonic kidney 293 (HEK-293) cells.We used the patch-clamp technique to study I KAS in HEK-293 cells transiently expressing human SK2 before and after amiodarone administration.Amiodarone inhibited IKAS in a dose-dependent manner (IC50, 2.67 ± 0.25 µM with 1 µM intrapipette Ca(2+)). Maximal inhibition was observed with 50 µM amiodarone which inhibited 85.6 ± 3.1% of IKAS induced with 1 µM intrapipette Ca(2+) (n = 3). IKAS inhibition by amiodarone was not voltage-dependent, but was Ca(2+)-dependent: 30 µM amiodarone inhibited 81.5±1.9% of I KAS induced with 1 µM Ca(2+) (n = 4), and 16.4±4.9% with 250 nM Ca(2+) (n = 5). Desethylamiodarone, a major metabolite of amiodarone, also exerts voltage-independent but Ca(2+) dependent inhibition of I KAS.Both amiodarone and desethylamiodarone inhibit I KAS at therapeutic concentrations. The inhibition is independent of time and voltage, but is dependent on the intracellular Ca(2+) concentration. SK2 current inhibition may in part underlie amiodarone's effects in preventing electrical storm in failing ventricles.http://europepmc.org/articles/PMC3726612?pdf=render |
| spellingShingle | Isik Turker Chih-Chieh Yu Po-Cheng Chang Zhenhui Chen Yoshiro Sohma Shien-Fong Lin Peng-Sheng Chen Tomohiko Ai Amiodarone inhibits apamin-sensitive potassium currents. PLoS ONE |
| title | Amiodarone inhibits apamin-sensitive potassium currents. |
| title_full | Amiodarone inhibits apamin-sensitive potassium currents. |
| title_fullStr | Amiodarone inhibits apamin-sensitive potassium currents. |
| title_full_unstemmed | Amiodarone inhibits apamin-sensitive potassium currents. |
| title_short | Amiodarone inhibits apamin-sensitive potassium currents. |
| title_sort | amiodarone inhibits apamin sensitive potassium currents |
| url | http://europepmc.org/articles/PMC3726612?pdf=render |
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