Regulation of the Cav1.2 cardiac channel by redox via modulation of CaM interaction with the channel
Although it has been well documented that redox can modulate Cav1.2 channel activity, the underlying mechanisms are not fully understood. In our study, we examined the effects of redox on Cav1.2 channel activity and on CaM interaction with the Cav1.2 α1 subunit. Dithiothreitol (DTT, 1 mM) in the cel...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-07-01
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| Series: | Journal of Pharmacological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861315001097 |
| _version_ | 1818367823783657472 |
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| author | Yu Sun Jianjun Xu Etsuko Minobe Shoken Shimoara Liying Hao Masaki Kameyama |
| author_facet | Yu Sun Jianjun Xu Etsuko Minobe Shoken Shimoara Liying Hao Masaki Kameyama |
| author_sort | Yu Sun |
| collection | DOAJ |
| description | Although it has been well documented that redox can modulate Cav1.2 channel activity, the underlying mechanisms are not fully understood. In our study, we examined the effects of redox on Cav1.2 channel activity and on CaM interaction with the Cav1.2 α1 subunit. Dithiothreitol (DTT, 1 mM) in the cell-attached mode decreased, while hydrogen peroxide (H2O2, 1 mM) increased channel activity to 72 and 303%, respectively. The effects of redox were maintained in the inside-out mode where channel activity was induced by CaM + ATP: DTT (1 mM) decreased, while H2O2 (1 mM) increased the channel activity. These results were mimicked by the thioredoxin and oxidized glutathione system. To test whether the redox state might determine channel activity by affecting the CaM interaction with the channel, we examined the effects of DTT and H2O2 on CaM binding to the N- and C-terminal fragments of the channel. We found that DTT concentration-dependently inhibited CaM binding to the C-terminus (IC50 37 μM), but H2O2 had no effect. Neither DTT nor H2O2 had an effect on CaM interaction with the N-terminus. These results suggest that redox-mediated regulation of the Cav1.2 channel is governed, at least partially, by modulation of the CaM interaction with the channel. |
| first_indexed | 2024-12-13T22:58:11Z |
| format | Article |
| id | doaj.art-59f027f48aee4e559695587c156e092a |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-13T22:58:11Z |
| publishDate | 2015-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-59f027f48aee4e559695587c156e092a2022-12-21T23:28:28ZengElsevierJournal of Pharmacological Sciences1347-86132015-07-01128313714310.1016/j.jphs.2015.06.003Regulation of the Cav1.2 cardiac channel by redox via modulation of CaM interaction with the channelYu Sun0Jianjun Xu1Etsuko Minobe2Shoken Shimoara3Liying Hao4Masaki Kameyama5Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, ChinaDepartment of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, JapanDepartment of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, JapanDepartment of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, JapanDepartment of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, ChinaDepartment of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, JapanAlthough it has been well documented that redox can modulate Cav1.2 channel activity, the underlying mechanisms are not fully understood. In our study, we examined the effects of redox on Cav1.2 channel activity and on CaM interaction with the Cav1.2 α1 subunit. Dithiothreitol (DTT, 1 mM) in the cell-attached mode decreased, while hydrogen peroxide (H2O2, 1 mM) increased channel activity to 72 and 303%, respectively. The effects of redox were maintained in the inside-out mode where channel activity was induced by CaM + ATP: DTT (1 mM) decreased, while H2O2 (1 mM) increased the channel activity. These results were mimicked by the thioredoxin and oxidized glutathione system. To test whether the redox state might determine channel activity by affecting the CaM interaction with the channel, we examined the effects of DTT and H2O2 on CaM binding to the N- and C-terminal fragments of the channel. We found that DTT concentration-dependently inhibited CaM binding to the C-terminus (IC50 37 μM), but H2O2 had no effect. Neither DTT nor H2O2 had an effect on CaM interaction with the N-terminus. These results suggest that redox-mediated regulation of the Cav1.2 channel is governed, at least partially, by modulation of the CaM interaction with the channel.http://www.sciencedirect.com/science/article/pii/S1347861315001097RedoxCav1.2 channelCalmodulinCardiac myocyteIon channel regulation |
| spellingShingle | Yu Sun Jianjun Xu Etsuko Minobe Shoken Shimoara Liying Hao Masaki Kameyama Regulation of the Cav1.2 cardiac channel by redox via modulation of CaM interaction with the channel Journal of Pharmacological Sciences Redox Cav1.2 channel Calmodulin Cardiac myocyte Ion channel regulation |
| title | Regulation of the Cav1.2 cardiac channel by redox via modulation of CaM interaction with the channel |
| title_full | Regulation of the Cav1.2 cardiac channel by redox via modulation of CaM interaction with the channel |
| title_fullStr | Regulation of the Cav1.2 cardiac channel by redox via modulation of CaM interaction with the channel |
| title_full_unstemmed | Regulation of the Cav1.2 cardiac channel by redox via modulation of CaM interaction with the channel |
| title_short | Regulation of the Cav1.2 cardiac channel by redox via modulation of CaM interaction with the channel |
| title_sort | regulation of the cav1 2 cardiac channel by redox via modulation of cam interaction with the channel |
| topic | Redox Cav1.2 channel Calmodulin Cardiac myocyte Ion channel regulation |
| url | http://www.sciencedirect.com/science/article/pii/S1347861315001097 |
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