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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,...

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Autores principales: Lee, Hyang Mi, Hahn, Sang June, Choi, Bok Hee
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
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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.
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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
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