Abstract
The effect of cyclosporin A (CsA), an immunosuppressant, on human ether-a-go-go-related gene (HERG) channel as it is expressed in human embryonic kidney cells was studied using a whole-cell, patch-clamp technique. CsA inhibited the HERG channel in a concentration-dependent manner, with an IC 50 value and a Hill coefficient of 3.17 μ M and 0.89, respectively. Pretreatment with cypermethrine, a calcineurin inhibitor, had no effect on the CsA-induced inhibition of the HERG channel. The CsA-induced inhibition of HERG channels was voltage-dependent, with a steep increase over the voltage range of the channel opening. However, the inhibition exhibited voltage independence over the voltage range of fully activated channels. CsA blocked the HERG channels predominantly in the open and inactivated states rather than in the closed state. Results of the present study suggest that CsA acts directly on the HERG channel as an open-channel blocker, and it acts independently of its effect on calcineurin activity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 291-297 |
| Number of pages | 7 |
| Journal | Korean Journal of Physiology and Pharmacology |
| Volume | 15 |
| Issue number | 5 |
| DOIs | |
| State | Published - Oct 1 2011 |
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Keywords
- Cyclosporin A
- HERG
- Immunosuppressant
- Long QT syndrome
- Open channel block
ASJC Scopus subject areas
- Physiology
- Pharmacology
Cite this
Inhibitory actions of HERG currents by the immunosuppressant drug cyclosporin A. / Lee, Seung Ho; Hahn, Sang June; Min, Gyesik; Kim, Jimok; Jo, Su Hyun; Choe, Han; Choi, Bok Hee.
In: Korean Journal of Physiology and Pharmacology, Vol. 15, No. 5, 01.10.2011, p. 291-297.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibitory actions of HERG currents by the immunosuppressant drug cyclosporin A
AU - Lee, Seung Ho
AU - Hahn, Sang June
AU - Min, Gyesik
AU - Kim, Jimok
AU - Jo, Su Hyun
AU - Choe, Han
AU - Choi, Bok Hee
PY - 2011/10/1
Y1 - 2011/10/1
N2 - The effect of cyclosporin A (CsA), an immunosuppressant, on human ether-a-go-go-related gene (HERG) channel as it is expressed in human embryonic kidney cells was studied using a whole-cell, patch-clamp technique. CsA inhibited the HERG channel in a concentration-dependent manner, with an IC 50 value and a Hill coefficient of 3.17 μ M and 0.89, respectively. Pretreatment with cypermethrine, a calcineurin inhibitor, had no effect on the CsA-induced inhibition of the HERG channel. The CsA-induced inhibition of HERG channels was voltage-dependent, with a steep increase over the voltage range of the channel opening. However, the inhibition exhibited voltage independence over the voltage range of fully activated channels. CsA blocked the HERG channels predominantly in the open and inactivated states rather than in the closed state. Results of the present study suggest that CsA acts directly on the HERG channel as an open-channel blocker, and it acts independently of its effect on calcineurin activity.
AB - The effect of cyclosporin A (CsA), an immunosuppressant, on human ether-a-go-go-related gene (HERG) channel as it is expressed in human embryonic kidney cells was studied using a whole-cell, patch-clamp technique. CsA inhibited the HERG channel in a concentration-dependent manner, with an IC 50 value and a Hill coefficient of 3.17 μ M and 0.89, respectively. Pretreatment with cypermethrine, a calcineurin inhibitor, had no effect on the CsA-induced inhibition of the HERG channel. The CsA-induced inhibition of HERG channels was voltage-dependent, with a steep increase over the voltage range of the channel opening. However, the inhibition exhibited voltage independence over the voltage range of fully activated channels. CsA blocked the HERG channels predominantly in the open and inactivated states rather than in the closed state. Results of the present study suggest that CsA acts directly on the HERG channel as an open-channel blocker, and it acts independently of its effect on calcineurin activity.
KW - Cyclosporin A
KW - HERG
KW - Immunosuppressant
KW - Long QT syndrome
KW - Open channel block
UR - http://www.scopus.com/inward/record.url?scp=81455128955&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=81455128955&partnerID=8YFLogxK
U2 - 10.4196/kjpp.2011.15.5.291
DO - 10.4196/kjpp.2011.15.5.291
M3 - Article
C2 - 22128262
AN - SCOPUS:81455128955
VL - 15
SP - 291
EP - 297
JO - Korean Journal of Physiology and Pharmacology
JF - Korean Journal of Physiology and Pharmacology
SN - 1226-4512
IS - 5
ER -