The inhibitory effects of bupivacaine, levobupivacaine, and ropivacaine on K2P (two-pore domain potassium) channel TREK-1

Hye Won Shin, Jeong Seop Soh, Heezoo Kim, Jinpyo Hong, Dong Ho Woo, Jun Young Heo, Eun Mi Hwang, Jae-Yong Park, Changjoon Lee

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purpose: Bupivacaine, levobupivacaine, and ropivacaine are amide local anesthetics. Levobupivacaine and ropivacaine are stereoisomers of bupivacaine and were developed to circumvent the bupivacaine's severe toxicity. The recently characterized background potassium channel, K2P TREK-1, is a well-known target for various local anesthetics. The purpose of study is to investigate the differences in inhibitory potency and stereoselectivity among bupivacaine, levobupivacaine, and ropivacaine on K2P TREK-1 channels overexpressed in COS-7 cells. Methods: We investigated the effects of bupivacaine, levobupivacaine, and ropivacaine (10, 50, 100, 200, and 400 μM) on TREK-1 channels expressed in COS-7 cells by using the whole cell patch clamp technique with a voltage ramp protocol ranging from -100 to 100 mV for 200 ms from a holding potential of -70 mV. Results: Bupivacaine, levobupivacaine, and ropivacaine showed reversible inhibition of TREK-1 channels in a concentration-dependent manner. The half-maximal inhibitory concentrations (IC50) of bupivacaine, levobupivacaine, and ropivacaine were 95.4 ± 14.6, 126.1 ± 24.5, and 402.7 ± 31.8 μM, respectively. IC50 values indicated a rank order of potency (bupivacaine > levobupivacaine > ropivacaine) with stereoselectivity. Hill coefficients were 0.84, 0.93, and 0.89 for bupivacaine, levobupivacaine, and ropivacaine, respectively. Conclusion: Inhibitory effects on TREK-1 channels by bupivacaine, levobupivacaine, and ropivacaine demonstrated stereoselectivity: bupivacaine was more potent than levobupivacaine and ropivacaine. Inhibition of TREK-1 channels and consecutive depolarization of the cell membrane by bupivacaine, levobupivacaine, and ropivacaine may contribute to the blockade of neuronal conduction and side effects.

Original languageEnglish
Pages (from-to)81-86
Number of pages6
JournalJournal of Anesthesia
Volume28
Issue number1
DOIs
Publication statusPublished - 2014 Feb 1

Fingerprint

Bupivacaine
COS Cells
Local Anesthetics
Inhibitory Concentration 50
Tandem Pore Domain Potassium Channels
potassium channel protein TREK-1
levobupivacaine
ropivacaine
Architectural Accessibility
Stereoisomerism
Patch-Clamp Techniques
Amides
Cell Membrane

Keywords

  • Bupivacaine
  • Levobupivacaine
  • Ropivacaine
  • TREK-1
  • Two-pore domain potassium channel

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

The inhibitory effects of bupivacaine, levobupivacaine, and ropivacaine on K2P (two-pore domain potassium) channel TREK-1. / Shin, Hye Won; Soh, Jeong Seop; Kim, Heezoo; Hong, Jinpyo; Woo, Dong Ho; Heo, Jun Young; Hwang, Eun Mi; Park, Jae-Yong; Lee, Changjoon.

In: Journal of Anesthesia, Vol. 28, No. 1, 01.02.2014, p. 81-86.

Research output: Contribution to journalArticle

Shin, Hye Won ; Soh, Jeong Seop ; Kim, Heezoo ; Hong, Jinpyo ; Woo, Dong Ho ; Heo, Jun Young ; Hwang, Eun Mi ; Park, Jae-Yong ; Lee, Changjoon. / The inhibitory effects of bupivacaine, levobupivacaine, and ropivacaine on K2P (two-pore domain potassium) channel TREK-1. In: Journal of Anesthesia. 2014 ; Vol. 28, No. 1. pp. 81-86.
@article{02bb37d16a3442da9de793862464e69e,
title = "The inhibitory effects of bupivacaine, levobupivacaine, and ropivacaine on K2P (two-pore domain potassium) channel TREK-1",
abstract = "Purpose: Bupivacaine, levobupivacaine, and ropivacaine are amide local anesthetics. Levobupivacaine and ropivacaine are stereoisomers of bupivacaine and were developed to circumvent the bupivacaine's severe toxicity. The recently characterized background potassium channel, K2P TREK-1, is a well-known target for various local anesthetics. The purpose of study is to investigate the differences in inhibitory potency and stereoselectivity among bupivacaine, levobupivacaine, and ropivacaine on K2P TREK-1 channels overexpressed in COS-7 cells. Methods: We investigated the effects of bupivacaine, levobupivacaine, and ropivacaine (10, 50, 100, 200, and 400 μM) on TREK-1 channels expressed in COS-7 cells by using the whole cell patch clamp technique with a voltage ramp protocol ranging from -100 to 100 mV for 200 ms from a holding potential of -70 mV. Results: Bupivacaine, levobupivacaine, and ropivacaine showed reversible inhibition of TREK-1 channels in a concentration-dependent manner. The half-maximal inhibitory concentrations (IC50) of bupivacaine, levobupivacaine, and ropivacaine were 95.4 ± 14.6, 126.1 ± 24.5, and 402.7 ± 31.8 μM, respectively. IC50 values indicated a rank order of potency (bupivacaine > levobupivacaine > ropivacaine) with stereoselectivity. Hill coefficients were 0.84, 0.93, and 0.89 for bupivacaine, levobupivacaine, and ropivacaine, respectively. Conclusion: Inhibitory effects on TREK-1 channels by bupivacaine, levobupivacaine, and ropivacaine demonstrated stereoselectivity: bupivacaine was more potent than levobupivacaine and ropivacaine. Inhibition of TREK-1 channels and consecutive depolarization of the cell membrane by bupivacaine, levobupivacaine, and ropivacaine may contribute to the blockade of neuronal conduction and side effects.",
keywords = "Bupivacaine, Levobupivacaine, Ropivacaine, TREK-1, Two-pore domain potassium channel",
author = "Shin, {Hye Won} and Soh, {Jeong Seop} and Heezoo Kim and Jinpyo Hong and Woo, {Dong Ho} and Heo, {Jun Young} and Hwang, {Eun Mi} and Jae-Yong Park and Changjoon Lee",
year = "2014",
month = "2",
day = "1",
doi = "10.1007/s00540-013-1661-1",
language = "English",
volume = "28",
pages = "81--86",
journal = "Journal of Anesthesia",
issn = "0913-8668",
publisher = "Springer Japan",
number = "1",

}

TY - JOUR

T1 - The inhibitory effects of bupivacaine, levobupivacaine, and ropivacaine on K2P (two-pore domain potassium) channel TREK-1

AU - Shin, Hye Won

AU - Soh, Jeong Seop

AU - Kim, Heezoo

AU - Hong, Jinpyo

AU - Woo, Dong Ho

AU - Heo, Jun Young

AU - Hwang, Eun Mi

AU - Park, Jae-Yong

AU - Lee, Changjoon

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Purpose: Bupivacaine, levobupivacaine, and ropivacaine are amide local anesthetics. Levobupivacaine and ropivacaine are stereoisomers of bupivacaine and were developed to circumvent the bupivacaine's severe toxicity. The recently characterized background potassium channel, K2P TREK-1, is a well-known target for various local anesthetics. The purpose of study is to investigate the differences in inhibitory potency and stereoselectivity among bupivacaine, levobupivacaine, and ropivacaine on K2P TREK-1 channels overexpressed in COS-7 cells. Methods: We investigated the effects of bupivacaine, levobupivacaine, and ropivacaine (10, 50, 100, 200, and 400 μM) on TREK-1 channels expressed in COS-7 cells by using the whole cell patch clamp technique with a voltage ramp protocol ranging from -100 to 100 mV for 200 ms from a holding potential of -70 mV. Results: Bupivacaine, levobupivacaine, and ropivacaine showed reversible inhibition of TREK-1 channels in a concentration-dependent manner. The half-maximal inhibitory concentrations (IC50) of bupivacaine, levobupivacaine, and ropivacaine were 95.4 ± 14.6, 126.1 ± 24.5, and 402.7 ± 31.8 μM, respectively. IC50 values indicated a rank order of potency (bupivacaine > levobupivacaine > ropivacaine) with stereoselectivity. Hill coefficients were 0.84, 0.93, and 0.89 for bupivacaine, levobupivacaine, and ropivacaine, respectively. Conclusion: Inhibitory effects on TREK-1 channels by bupivacaine, levobupivacaine, and ropivacaine demonstrated stereoselectivity: bupivacaine was more potent than levobupivacaine and ropivacaine. Inhibition of TREK-1 channels and consecutive depolarization of the cell membrane by bupivacaine, levobupivacaine, and ropivacaine may contribute to the blockade of neuronal conduction and side effects.

AB - Purpose: Bupivacaine, levobupivacaine, and ropivacaine are amide local anesthetics. Levobupivacaine and ropivacaine are stereoisomers of bupivacaine and were developed to circumvent the bupivacaine's severe toxicity. The recently characterized background potassium channel, K2P TREK-1, is a well-known target for various local anesthetics. The purpose of study is to investigate the differences in inhibitory potency and stereoselectivity among bupivacaine, levobupivacaine, and ropivacaine on K2P TREK-1 channels overexpressed in COS-7 cells. Methods: We investigated the effects of bupivacaine, levobupivacaine, and ropivacaine (10, 50, 100, 200, and 400 μM) on TREK-1 channels expressed in COS-7 cells by using the whole cell patch clamp technique with a voltage ramp protocol ranging from -100 to 100 mV for 200 ms from a holding potential of -70 mV. Results: Bupivacaine, levobupivacaine, and ropivacaine showed reversible inhibition of TREK-1 channels in a concentration-dependent manner. The half-maximal inhibitory concentrations (IC50) of bupivacaine, levobupivacaine, and ropivacaine were 95.4 ± 14.6, 126.1 ± 24.5, and 402.7 ± 31.8 μM, respectively. IC50 values indicated a rank order of potency (bupivacaine > levobupivacaine > ropivacaine) with stereoselectivity. Hill coefficients were 0.84, 0.93, and 0.89 for bupivacaine, levobupivacaine, and ropivacaine, respectively. Conclusion: Inhibitory effects on TREK-1 channels by bupivacaine, levobupivacaine, and ropivacaine demonstrated stereoselectivity: bupivacaine was more potent than levobupivacaine and ropivacaine. Inhibition of TREK-1 channels and consecutive depolarization of the cell membrane by bupivacaine, levobupivacaine, and ropivacaine may contribute to the blockade of neuronal conduction and side effects.

KW - Bupivacaine

KW - Levobupivacaine

KW - Ropivacaine

KW - TREK-1

KW - Two-pore domain potassium channel

UR - http://www.scopus.com/inward/record.url?scp=84894414794&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84894414794&partnerID=8YFLogxK

U2 - 10.1007/s00540-013-1661-1

DO - 10.1007/s00540-013-1661-1

M3 - Article

C2 - 23797625

AN - SCOPUS:84894414794

VL - 28

SP - 81

EP - 86

JO - Journal of Anesthesia

JF - Journal of Anesthesia

SN - 0913-8668

IS - 1

ER -