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 language | English |
|---|---|
| Pages (from-to) | 81-86 |
| Number of pages | 6 |
| Journal | Journal of Anesthesia |
| Volume | 28 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2014 Feb 1 |
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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 journal › Article
}
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 -