Open channel block of Kv1.3 by rosiglitazone and troglitazone: Kv1.3 as the pharmacological target for rosiglitazone

Hye Sook Ahn; Sung Eun Kim; Hyun Jong Jang; Myung Jun Kim; Duck Joo Rhie; Shin Hee Yoon; Yang Hyeok Jo; Myung Suk Kim; Ki Wug Sung; Seong Yun Kim; Sang June Hahn

doi:10.1007/s00210-006-0118-6

Open channel block of Kv1.3 by rosiglitazone and troglitazone: Kv1.3 as the pharmacological target for rosiglitazone

Hye Sook Ahn
, Sung Eun Kim
, Hyun Jong Jang
, Myung Jun Kim
, Duck Joo Rhie
, Shin Hee Yoon
, Yang Hyeok Jo
, Myung Suk Kim
, Ki Wug Sung
, Seong Yun Kim
, Sang June Hahn

Department of Physiology

The Catholic University of Korea

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

The effects of rosiglitazone and troglitazone were examined on cloned Kv1.3 channels stably expressed in Chinese hamster ovary cells using the whole-cell configuration of the patch-clamp technique. Rosiglitazone decreased the Kv1.3 currents and accelerated the decay rate of current inactivation in a concentration-dependent manner with an IC₅₀ of 18.6 μM. These effects were reversible after washout of the drug. Troglitazone caused the block of Kv1.3 with a similar pattern but was five times more potent than rosiglitazone with an IC₅₀ of 3.5 μM. The block of Kv1.3 by rosiglitazone and troglitazone was voltage-dependent at a membrane potential coinciding with the activation of the channels. Both drugs decreased the tail current amplitude and slowed the deactivation process of Kv1.3, resulting in a tail crossover phenomenon. These results indicate that rosiglitazone and troglitazone block the open state of Kv1.3 channels, suggesting that it is an important pharmacological target for rosiglitazone as a potent blocker of Kv1.3 channels.

Original language	English
Pages (from-to)	305-309
Number of pages	5
Journal	Naunyn-Schmiedeberg's Archives of Pharmacology
Volume	374
Issue number	4
DOIs	https://doi.org/10.1007/s00210-006-0118-6
State	Published - Jan 2007

Bibliographical note

Funding Information:
Acknowledgements We thank Dr. Kaczmarek (Yale University School of Medicine, USA) for the Kv1.3 transfected CHO cells. This work was supported by a grant from the Medical Research Center, Korea Science and Engineering Foundation, Republic of Korea (R13-2002-005-01002-0).

Keywords

Insulin sensitizer
Thiazolidinedione
Voltage-gated K channel

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10.1007/s00210-006-0118-6

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title = "Open channel block of Kv1.3 by rosiglitazone and troglitazone: Kv1.3 as the pharmacological target for rosiglitazone",

abstract = "The effects of rosiglitazone and troglitazone were examined on cloned Kv1.3 channels stably expressed in Chinese hamster ovary cells using the whole-cell configuration of the patch-clamp technique. Rosiglitazone decreased the Kv1.3 currents and accelerated the decay rate of current inactivation in a concentration-dependent manner with an IC50 of 18.6 μM. These effects were reversible after washout of the drug. Troglitazone caused the block of Kv1.3 with a similar pattern but was five times more potent than rosiglitazone with an IC50 of 3.5 μM. The block of Kv1.3 by rosiglitazone and troglitazone was voltage-dependent at a membrane potential coinciding with the activation of the channels. Both drugs decreased the tail current amplitude and slowed the deactivation process of Kv1.3, resulting in a tail crossover phenomenon. These results indicate that rosiglitazone and troglitazone block the open state of Kv1.3 channels, suggesting that it is an important pharmacological target for rosiglitazone as a potent blocker of Kv1.3 channels.",

keywords = "Insulin sensitizer, Thiazolidinedione, Voltage-gated K channel",

author = "Ahn, \{Hye Sook\} and Kim, \{Sung Eun\} and Jang, \{Hyun Jong\} and Kim, \{Myung Jun\} and Rhie, \{Duck Joo\} and Yoon, \{Shin Hee\} and Jo, \{Yang Hyeok\} and Kim, \{Myung Suk\} and Sung, \{Ki Wug\} and Kim, \{Seong Yun\} and Hahn, \{Sang June\}",

note = "Funding Information: Acknowledgements We thank Dr. Kaczmarek (Yale University School of Medicine, USA) for the Kv1.3 transfected CHO cells. This work was supported by a grant from the Medical Research Center, Korea Science and Engineering Foundation, Republic of Korea (R13-2002-005-01002-0).",

year = "2007",

month = jan,

doi = "10.1007/s00210-006-0118-6",

language = "English",

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journal = "Naunyn-Schmiedeberg's Archives of Pharmacology",

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T2 - Kv1.3 as the pharmacological target for rosiglitazone

AU - Ahn, Hye Sook

AU - Kim, Sung Eun

AU - Jang, Hyun Jong

AU - Kim, Myung Jun

AU - Rhie, Duck Joo

AU - Yoon, Shin Hee

AU - Jo, Yang Hyeok

AU - Kim, Myung Suk

AU - Sung, Ki Wug

AU - Kim, Seong Yun

AU - Hahn, Sang June

N1 - Funding Information: Acknowledgements We thank Dr. Kaczmarek (Yale University School of Medicine, USA) for the Kv1.3 transfected CHO cells. This work was supported by a grant from the Medical Research Center, Korea Science and Engineering Foundation, Republic of Korea (R13-2002-005-01002-0).

PY - 2007/1

Y1 - 2007/1

N2 - The effects of rosiglitazone and troglitazone were examined on cloned Kv1.3 channels stably expressed in Chinese hamster ovary cells using the whole-cell configuration of the patch-clamp technique. Rosiglitazone decreased the Kv1.3 currents and accelerated the decay rate of current inactivation in a concentration-dependent manner with an IC50 of 18.6 μM. These effects were reversible after washout of the drug. Troglitazone caused the block of Kv1.3 with a similar pattern but was five times more potent than rosiglitazone with an IC50 of 3.5 μM. The block of Kv1.3 by rosiglitazone and troglitazone was voltage-dependent at a membrane potential coinciding with the activation of the channels. Both drugs decreased the tail current amplitude and slowed the deactivation process of Kv1.3, resulting in a tail crossover phenomenon. These results indicate that rosiglitazone and troglitazone block the open state of Kv1.3 channels, suggesting that it is an important pharmacological target for rosiglitazone as a potent blocker of Kv1.3 channels.

AB - The effects of rosiglitazone and troglitazone were examined on cloned Kv1.3 channels stably expressed in Chinese hamster ovary cells using the whole-cell configuration of the patch-clamp technique. Rosiglitazone decreased the Kv1.3 currents and accelerated the decay rate of current inactivation in a concentration-dependent manner with an IC50 of 18.6 μM. These effects were reversible after washout of the drug. Troglitazone caused the block of Kv1.3 with a similar pattern but was five times more potent than rosiglitazone with an IC50 of 3.5 μM. The block of Kv1.3 by rosiglitazone and troglitazone was voltage-dependent at a membrane potential coinciding with the activation of the channels. Both drugs decreased the tail current amplitude and slowed the deactivation process of Kv1.3, resulting in a tail crossover phenomenon. These results indicate that rosiglitazone and troglitazone block the open state of Kv1.3 channels, suggesting that it is an important pharmacological target for rosiglitazone as a potent blocker of Kv1.3 channels.

KW - Insulin sensitizer

KW - Thiazolidinedione

KW - Voltage-gated K channel

UR - https://www.scopus.com/pages/publications/33846221869

U2 - 10.1007/s00210-006-0118-6

DO - 10.1007/s00210-006-0118-6

M3 - Article

C2 - 17119927

AN - SCOPUS:33846221869

SN - 0028-1298

VL - 374

SP - 305

EP - 309

JO - Naunyn-Schmiedeberg's Archives of Pharmacology

JF - Naunyn-Schmiedeberg's Archives of Pharmacology

IS - 4

ER -

Open channel block of Kv1.3 by rosiglitazone and troglitazone: Kv1.3 as the pharmacological target for rosiglitazone

Abstract

Bibliographical note

Keywords

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