Inhibition of cardiac Kv1.5 potassium current by the anesthetic midazolam: mode of action
Nadine Vonderlin,1 Fathima Fischer,1 Edgar Zitron,1,2 Claudia Seyler,1 Daniel Scherer,1 Dierk Thomas,1,2 Hugo A Katus,1,2 Eberhard P Scholz1 1Department of Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany; 2German Centre for Cardiovascular Research (DZHK), Partner Site Hei...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2014-11-01
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| Series: | Drug Design, Development and Therapy |
| Online Access: | http://www.dovepress.com/inhibition-of-cardiac-kv15-potassium-current-by-the-anesthetic-midazol-peer-reviewed-article-DDDT |
| _version_ | 1811261709632929792 |
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| author | Vonderlin N Fischer F Zitron E Seyler C Scherer D Thomas D Katus HA Scholz EP |
| author_facet | Vonderlin N Fischer F Zitron E Seyler C Scherer D Thomas D Katus HA Scholz EP |
| author_sort | Vonderlin N |
| collection | DOAJ |
| description | Nadine Vonderlin,1 Fathima Fischer,1 Edgar Zitron,1,2 Claudia Seyler,1 Daniel Scherer,1 Dierk Thomas,1,2 Hugo A Katus,1,2 Eberhard P Scholz1 1Department of Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany; 2German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Heidelberg, GermanyAbstract: Midazolam is a short-acting benzodiazepine that is widely used in anesthesia. Despite its widespread clinical use, detailed information about cardiac side effects of midazolam is largely lacking. Using the double-electrode voltage clamp technique, we studied pharmacological effects of midazolam on heterologously expressed Kv1.5 channels underlying atrial repolarizing current IKur. Midazolam dose-dependently inhibited Kv1.5 current, yielding an IC50 of 17 µM in an HEK cell line and an IC50 of 104 µM in Xenopus oocytes. We further showed that midazolam did not affect the half-maximal activation voltage of Kv1.5 channels. However, a small negative shift of the inactivation curve could be observed. Midazolam acted as a typical open-channel inhibitor with rapid onset of block and without frequency dependence of block. Taken together, midazolam is an open channel inhibitor of cardiac Kv1.5 channels. These data add to the current understanding of the pharmacological profile of midazolam.Keywords: anesthetics, potassium channels, pharmacology |
| first_indexed | 2024-04-12T19:10:34Z |
| format | Article |
| id | doaj.art-d4f5b8fd12a54833a6f85b2f1bd22242 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-04-12T19:10:34Z |
| publishDate | 2014-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-d4f5b8fd12a54833a6f85b2f1bd222422022-12-22T03:19:54ZengDove Medical PressDrug Design, Development and Therapy1177-88812014-11-012014default2263227119075Inhibition of cardiac Kv1.5 potassium current by the anesthetic midazolam: mode of actionVonderlin NFischer FZitron ESeyler CScherer DThomas DKatus HAScholz EPNadine Vonderlin,1 Fathima Fischer,1 Edgar Zitron,1,2 Claudia Seyler,1 Daniel Scherer,1 Dierk Thomas,1,2 Hugo A Katus,1,2 Eberhard P Scholz1 1Department of Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany; 2German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Heidelberg, GermanyAbstract: Midazolam is a short-acting benzodiazepine that is widely used in anesthesia. Despite its widespread clinical use, detailed information about cardiac side effects of midazolam is largely lacking. Using the double-electrode voltage clamp technique, we studied pharmacological effects of midazolam on heterologously expressed Kv1.5 channels underlying atrial repolarizing current IKur. Midazolam dose-dependently inhibited Kv1.5 current, yielding an IC50 of 17 µM in an HEK cell line and an IC50 of 104 µM in Xenopus oocytes. We further showed that midazolam did not affect the half-maximal activation voltage of Kv1.5 channels. However, a small negative shift of the inactivation curve could be observed. Midazolam acted as a typical open-channel inhibitor with rapid onset of block and without frequency dependence of block. Taken together, midazolam is an open channel inhibitor of cardiac Kv1.5 channels. These data add to the current understanding of the pharmacological profile of midazolam.Keywords: anesthetics, potassium channels, pharmacologyhttp://www.dovepress.com/inhibition-of-cardiac-kv15-potassium-current-by-the-anesthetic-midazol-peer-reviewed-article-DDDT |
| spellingShingle | Vonderlin N Fischer F Zitron E Seyler C Scherer D Thomas D Katus HA Scholz EP Inhibition of cardiac Kv1.5 potassium current by the anesthetic midazolam: mode of action Drug Design, Development and Therapy |
| title | Inhibition of cardiac Kv1.5 potassium current by the anesthetic midazolam: mode of action |
| title_full | Inhibition of cardiac Kv1.5 potassium current by the anesthetic midazolam: mode of action |
| title_fullStr | Inhibition of cardiac Kv1.5 potassium current by the anesthetic midazolam: mode of action |
| title_full_unstemmed | Inhibition of cardiac Kv1.5 potassium current by the anesthetic midazolam: mode of action |
| title_short | Inhibition of cardiac Kv1.5 potassium current by the anesthetic midazolam: mode of action |
| title_sort | inhibition of cardiac kv1 5 potassium current by the anesthetic midazolam mode of action |
| url | http://www.dovepress.com/inhibition-of-cardiac-kv15-potassium-current-by-the-anesthetic-midazol-peer-reviewed-article-DDDT |
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