Eintrag weiter verarbeiten
Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels
Gespeichert in:
| Zeitschriftentitel: | British Journal of Pharmacology |
|---|---|
| Personen und Körperschaften: | , , |
| In: | British Journal of Pharmacology, 167, 2012, 6, S. 1378-1388 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
|
| Schlagwörter: |
| author_facet |
Nikouee, Azadeh Janbein, Malika Grissmer, Stephan Nikouee, Azadeh Janbein, Malika Grissmer, Stephan |
|---|---|
| author |
Nikouee, Azadeh Janbein, Malika Grissmer, Stephan |
| spellingShingle |
Nikouee, Azadeh Janbein, Malika Grissmer, Stephan British Journal of Pharmacology Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels Pharmacology |
| author_sort |
nikouee, azadeh |
| spelling |
Nikouee, Azadeh Janbein, Malika Grissmer, Stephan 0007-1188 1476-5381 Wiley Pharmacology http://dx.doi.org/10.1111/j.1476-5381.2012.02092.x <jats:p><jats:bold>BACKGROUND AND PURPOSE</jats:bold> T‐cells usually express voltage‐gated K<jats:sub>v</jats:sub>1.3 channels. These channels are distinguished by their typical C‐type inactivation. Therefore, to be able to rationally design drugs specific for the C‐type inactivation state that may have therapeutic value in autoimmune disease therapy, it is necessary to identify those amino acids that are accessible for drug binding in C‐type inactivated channels.</jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH</jats:bold> The influence of 2‐aminoethylmethanethiosulphonate (MTSEA) on currents through wild‐type human K<jats:sub>v</jats:sub>1.3 (<jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3) and three mutant channels, <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_L418C, <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_T419C and <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_I420C, in the closed, open and inactivated states was investigated by the patch‐clamp technique.</jats:p><jats:p><jats:bold>KEY RESULTS</jats:bold> Currents through <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_L418C and <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_T419C channels were irreversibly reduced after the external application of MTSEA in the open state but not in the inactivated and closed states. Currents through <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_I420C channels were irreversibly reduced in the open and inactivated states but not in the closed state. In the presence of verapamil, the MTSEA modification of <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_T419C and <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_I420C channels was prevented, while the MTSEA modification of <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_L418C channels was unaffected.</jats:p><jats:p><jats:bold>CONCLUSION AND IMPLICATIONS</jats:bold> From our experiments, we conclude that the activation gate of all mutant channels must be open for modification by MTSEA and must also be open during inactivation. In addition, the relative movement of the S6 segments that occur during C‐type inactivation includes a movement of the side chains of the amino acids at positions 418 and 419 away from the pore lining. Furthermore, the overlapping binding site for MTSEA and verapamil does not include position 418 in <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3 channels.</jats:p> Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on <i>h</i>K<sub>v</sub>1.3 channels British Journal of Pharmacology |
| doi_str_mv |
10.1111/j.1476-5381.2012.02092.x |
| facet_avail |
Online Free |
| finc_class_facet |
Chemie und Pharmazie |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMS9qLjE0NzYtNTM4MS4yMDEyLjAyMDkyLng |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMS9qLjE0NzYtNTM4MS4yMDEyLjAyMDkyLng |
| institution |
DE-Bn3 DE-Brt1 DE-D161 DE-Zwi2 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 |
| imprint |
Wiley, 2012 |
| imprint_str_mv |
Wiley, 2012 |
| issn |
0007-1188 1476-5381 |
| issn_str_mv |
0007-1188 1476-5381 |
| language |
English |
| mega_collection |
Wiley (CrossRef) |
| match_str |
nikouee2012verapamilandstatedependenteffectof2aminoethylmethanethiosulphonatemtseaonhkv13channels |
| publishDateSort |
2012 |
| publisher |
Wiley |
| recordtype |
ai |
| record_format |
ai |
| series |
British Journal of Pharmacology |
| source_id |
49 |
| title |
Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels |
| title_unstemmed |
Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels |
| title_full |
Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels |
| title_fullStr |
Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels |
| title_full_unstemmed |
Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels |
| title_short |
Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels |
| title_sort |
verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (mtsea) on <i>h</i>k<sub>v</sub>1.3 channels |
| topic |
Pharmacology |
| url |
http://dx.doi.org/10.1111/j.1476-5381.2012.02092.x |
| publishDate |
2012 |
| physical |
1378-1388 |
| description |
<jats:p><jats:bold>BACKGROUND AND PURPOSE</jats:bold> T‐cells usually express voltage‐gated K<jats:sub>v</jats:sub>1.3 channels. These channels are distinguished by their typical C‐type inactivation. Therefore, to be able to rationally design drugs specific for the C‐type inactivation state that may have therapeutic value in autoimmune disease therapy, it is necessary to identify those amino acids that are accessible for drug binding in C‐type inactivated channels.</jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH</jats:bold> The influence of 2‐aminoethylmethanethiosulphonate (MTSEA) on currents through wild‐type human K<jats:sub>v</jats:sub>1.3 (<jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3) and three mutant channels, <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_L418C, <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_T419C and <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_I420C, in the closed, open and inactivated states was investigated by the patch‐clamp technique.</jats:p><jats:p><jats:bold>KEY RESULTS</jats:bold> Currents through <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_L418C and <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_T419C channels were irreversibly reduced after the external application of MTSEA in the open state but not in the inactivated and closed states. Currents through <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_I420C channels were irreversibly reduced in the open and inactivated states but not in the closed state. In the presence of verapamil, the MTSEA modification of <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_T419C and <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_I420C channels was prevented, while the MTSEA modification of <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_L418C channels was unaffected.</jats:p><jats:p><jats:bold>CONCLUSION AND IMPLICATIONS</jats:bold> From our experiments, we conclude that the activation gate of all mutant channels must be open for modification by MTSEA and must also be open during inactivation. In addition, the relative movement of the S6 segments that occur during C‐type inactivation includes a movement of the side chains of the amino acids at positions 418 and 419 away from the pore lining. Furthermore, the overlapping binding site for MTSEA and verapamil does not include position 418 in <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3 channels.</jats:p> |
| container_issue |
6 |
| container_start_page |
1378 |
| container_title |
British Journal of Pharmacology |
| container_volume |
167 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792336427806097421 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T15:00:16.165Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Verapamil%E2%80%90+and+state%E2%80%90dependent+effect+of+2%E2%80%90aminoethylmethanethiosulphonate+%28MTSEA%29+on+hKv1.3+channels&rft.date=2012-11-01&genre=article&issn=1476-5381&volume=167&issue=6&spage=1378&epage=1388&pages=1378-1388&jtitle=British+Journal+of+Pharmacology&atitle=Verapamil%E2%80%90+and+state%E2%80%90dependent+effect+of+2%E2%80%90aminoethylmethanethiosulphonate+%28MTSEA%29+on+%3Ci%3Eh%3C%2Fi%3EK%3Csub%3Ev%3C%2Fsub%3E1.3+channels&aulast=Grissmer&aufirst=Stephan&rft_id=info%3Adoi%2F10.1111%2Fj.1476-5381.2012.02092.x&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792336427806097421 |
| author | Nikouee, Azadeh, Janbein, Malika, Grissmer, Stephan |
| author_facet | Nikouee, Azadeh, Janbein, Malika, Grissmer, Stephan, Nikouee, Azadeh, Janbein, Malika, Grissmer, Stephan |
| author_sort | nikouee, azadeh |
| container_issue | 6 |
| container_start_page | 1378 |
| container_title | British Journal of Pharmacology |
| container_volume | 167 |
| description | <jats:p><jats:bold>BACKGROUND AND PURPOSE</jats:bold> T‐cells usually express voltage‐gated K<jats:sub>v</jats:sub>1.3 channels. These channels are distinguished by their typical C‐type inactivation. Therefore, to be able to rationally design drugs specific for the C‐type inactivation state that may have therapeutic value in autoimmune disease therapy, it is necessary to identify those amino acids that are accessible for drug binding in C‐type inactivated channels.</jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH</jats:bold> The influence of 2‐aminoethylmethanethiosulphonate (MTSEA) on currents through wild‐type human K<jats:sub>v</jats:sub>1.3 (<jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3) and three mutant channels, <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_L418C, <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_T419C and <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_I420C, in the closed, open and inactivated states was investigated by the patch‐clamp technique.</jats:p><jats:p><jats:bold>KEY RESULTS</jats:bold> Currents through <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_L418C and <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_T419C channels were irreversibly reduced after the external application of MTSEA in the open state but not in the inactivated and closed states. Currents through <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_I420C channels were irreversibly reduced in the open and inactivated states but not in the closed state. In the presence of verapamil, the MTSEA modification of <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_T419C and <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_I420C channels was prevented, while the MTSEA modification of <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_L418C channels was unaffected.</jats:p><jats:p><jats:bold>CONCLUSION AND IMPLICATIONS</jats:bold> From our experiments, we conclude that the activation gate of all mutant channels must be open for modification by MTSEA and must also be open during inactivation. In addition, the relative movement of the S6 segments that occur during C‐type inactivation includes a movement of the side chains of the amino acids at positions 418 and 419 away from the pore lining. Furthermore, the overlapping binding site for MTSEA and verapamil does not include position 418 in <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3 channels.</jats:p> |
| doi_str_mv | 10.1111/j.1476-5381.2012.02092.x |
| facet_avail | Online, Free |
| finc_class_facet | Chemie und Pharmazie |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMS9qLjE0NzYtNTM4MS4yMDEyLjAyMDkyLng |
| imprint | Wiley, 2012 |
| imprint_str_mv | Wiley, 2012 |
| institution | DE-Bn3, DE-Brt1, DE-D161, DE-Zwi2, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275 |
| issn | 0007-1188, 1476-5381 |
| issn_str_mv | 0007-1188, 1476-5381 |
| language | English |
| last_indexed | 2024-03-01T15:00:16.165Z |
| match_str | nikouee2012verapamilandstatedependenteffectof2aminoethylmethanethiosulphonatemtseaonhkv13channels |
| mega_collection | Wiley (CrossRef) |
| physical | 1378-1388 |
| publishDate | 2012 |
| publishDateSort | 2012 |
| publisher | Wiley |
| record_format | ai |
| recordtype | ai |
| series | British Journal of Pharmacology |
| source_id | 49 |
| spelling | Nikouee, Azadeh Janbein, Malika Grissmer, Stephan 0007-1188 1476-5381 Wiley Pharmacology http://dx.doi.org/10.1111/j.1476-5381.2012.02092.x <jats:p><jats:bold>BACKGROUND AND PURPOSE</jats:bold> T‐cells usually express voltage‐gated K<jats:sub>v</jats:sub>1.3 channels. These channels are distinguished by their typical C‐type inactivation. Therefore, to be able to rationally design drugs specific for the C‐type inactivation state that may have therapeutic value in autoimmune disease therapy, it is necessary to identify those amino acids that are accessible for drug binding in C‐type inactivated channels.</jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH</jats:bold> The influence of 2‐aminoethylmethanethiosulphonate (MTSEA) on currents through wild‐type human K<jats:sub>v</jats:sub>1.3 (<jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3) and three mutant channels, <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_L418C, <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_T419C and <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_I420C, in the closed, open and inactivated states was investigated by the patch‐clamp technique.</jats:p><jats:p><jats:bold>KEY RESULTS</jats:bold> Currents through <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_L418C and <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_T419C channels were irreversibly reduced after the external application of MTSEA in the open state but not in the inactivated and closed states. Currents through <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_I420C channels were irreversibly reduced in the open and inactivated states but not in the closed state. In the presence of verapamil, the MTSEA modification of <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_T419C and <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_I420C channels was prevented, while the MTSEA modification of <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3_L418C channels was unaffected.</jats:p><jats:p><jats:bold>CONCLUSION AND IMPLICATIONS</jats:bold> From our experiments, we conclude that the activation gate of all mutant channels must be open for modification by MTSEA and must also be open during inactivation. In addition, the relative movement of the S6 segments that occur during C‐type inactivation includes a movement of the side chains of the amino acids at positions 418 and 419 away from the pore lining. Furthermore, the overlapping binding site for MTSEA and verapamil does not include position 418 in <jats:italic>h</jats:italic>K<jats:sub>v</jats:sub>1.3 channels.</jats:p> Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on <i>h</i>K<sub>v</sub>1.3 channels British Journal of Pharmacology |
| spellingShingle | Nikouee, Azadeh, Janbein, Malika, Grissmer, Stephan, British Journal of Pharmacology, Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels, Pharmacology |
| title | Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels |
| title_full | Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels |
| title_fullStr | Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels |
| title_full_unstemmed | Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels |
| title_short | Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels |
| title_sort | verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (mtsea) on <i>h</i>k<sub>v</sub>1.3 channels |
| title_unstemmed | Verapamil‐ and state‐dependent effect of 2‐aminoethylmethanethiosulphonate (MTSEA) on hKv1.3 channels |
| topic | Pharmacology |
| url | http://dx.doi.org/10.1111/j.1476-5381.2012.02092.x |