Cargando…
The antidiabetic drug rosiglitazone blocks Kv1.5 potassium channels in an open state
An antidiabetic drug, rosiglitazone is a member of the drug class of thiazolidinedione. Although restrictions on use due to the possibility of heart toxicity have been removed, it is still a drug that is concerned about side effects on the heart. We here examined, using Chinese hamster ovary cells,...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Physiological Society and The Korean Society of Pharmacology
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8890944/ https://www.ncbi.nlm.nih.gov/pubmed/35203063 http://dx.doi.org/10.4196/kjpp.2022.26.2.135 |
_version_ | 1784661760971636736 |
---|---|
author | Lee, Hyang Mi Hahn, Sang June Choi, Bok Hee |
author_facet | Lee, Hyang Mi Hahn, Sang June Choi, Bok Hee |
author_sort | Lee, Hyang Mi |
collection | PubMed |
description | An antidiabetic drug, rosiglitazone is a member of the drug class of thiazolidinedione. Although restrictions on use due to the possibility of heart toxicity have been removed, it is still a drug that is concerned about side effects on the heart. We here examined, using Chinese hamster ovary cells, the action of rosiglitazone on Kv1.5 channels, which is a major determinant of the duration of cardiac action potential. Rosiglitazone rapidly and reversibly inhibited Kv1.5 currents in a concentration-dependent manner (IC(50) = 18.9 µM) and accelerated the decay of Kv1.5 currents without modifying the activation kinetics. In addition, the deactivation of Kv1.5 current, assayed with tail current, was slowed by the drug. All of the results as well as the use-dependence of the rosiglitazone-mediated blockade indicate that rosiglitazone acts on Kv1.5 channels as an open channel blocker. This study suggests that the cardiac side effects of rosiglitazone might be mediated in part by suppression of Kv1.5 channels, and therefore, raises a concern of using the drug for diabetic therapeutics. |
format | Online Article Text |
id | pubmed-8890944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Korean Physiological Society and The Korean Society of Pharmacology |
record_format | MEDLINE/PubMed |
spelling | pubmed-88909442022-03-10 The antidiabetic drug rosiglitazone blocks Kv1.5 potassium channels in an open state Lee, Hyang Mi Hahn, Sang June Choi, Bok Hee Korean J Physiol Pharmacol Original Article An antidiabetic drug, rosiglitazone is a member of the drug class of thiazolidinedione. Although restrictions on use due to the possibility of heart toxicity have been removed, it is still a drug that is concerned about side effects on the heart. We here examined, using Chinese hamster ovary cells, the action of rosiglitazone on Kv1.5 channels, which is a major determinant of the duration of cardiac action potential. Rosiglitazone rapidly and reversibly inhibited Kv1.5 currents in a concentration-dependent manner (IC(50) = 18.9 µM) and accelerated the decay of Kv1.5 currents without modifying the activation kinetics. In addition, the deactivation of Kv1.5 current, assayed with tail current, was slowed by the drug. All of the results as well as the use-dependence of the rosiglitazone-mediated blockade indicate that rosiglitazone acts on Kv1.5 channels as an open channel blocker. This study suggests that the cardiac side effects of rosiglitazone might be mediated in part by suppression of Kv1.5 channels, and therefore, raises a concern of using the drug for diabetic therapeutics. The Korean Physiological Society and The Korean Society of Pharmacology 2022-03-01 2022-03-01 /pmc/articles/PMC8890944/ /pubmed/35203063 http://dx.doi.org/10.4196/kjpp.2022.26.2.135 Text en Copyright © Korean J Physiol Pharmacol https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Lee, Hyang Mi Hahn, Sang June Choi, Bok Hee The antidiabetic drug rosiglitazone blocks Kv1.5 potassium channels in an open state |
title | The antidiabetic drug rosiglitazone blocks Kv1.5 potassium channels in an open state |
title_full | The antidiabetic drug rosiglitazone blocks Kv1.5 potassium channels in an open state |
title_fullStr | The antidiabetic drug rosiglitazone blocks Kv1.5 potassium channels in an open state |
title_full_unstemmed | The antidiabetic drug rosiglitazone blocks Kv1.5 potassium channels in an open state |
title_short | The antidiabetic drug rosiglitazone blocks Kv1.5 potassium channels in an open state |
title_sort | antidiabetic drug rosiglitazone blocks kv1.5 potassium channels in an open state |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8890944/ https://www.ncbi.nlm.nih.gov/pubmed/35203063 http://dx.doi.org/10.4196/kjpp.2022.26.2.135 |
work_keys_str_mv | AT leehyangmi theantidiabeticdrugrosiglitazoneblockskv15potassiumchannelsinanopenstate AT hahnsangjune theantidiabeticdrugrosiglitazoneblockskv15potassiumchannelsinanopenstate AT choibokhee theantidiabeticdrugrosiglitazoneblockskv15potassiumchannelsinanopenstate AT leehyangmi antidiabeticdrugrosiglitazoneblockskv15potassiumchannelsinanopenstate AT hahnsangjune antidiabeticdrugrosiglitazoneblockskv15potassiumchannelsinanopenstate AT choibokhee antidiabeticdrugrosiglitazoneblockskv15potassiumchannelsinanopenstate |