Shin, Hye Won Soh, Jeong Seop Kim, Hee Zoo Hong, Jinpyo Woo, Dong Ho Heo, Jun Young Hwang, Eun Mi Park, Jae-Yong Lee, C. Justin 2024-01-20T10:32:26Z 2024-01-20T10:32:26Z 2021-09-05 2014-02 0913-8668 https://pubs.kist.re.kr/handle/201004/127158 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, K-2P 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 K-2P TREK-1 channels overexpressed in COS-7 cells. We investigated the effects of bupivacaine, levobupivacaine, and ropivacaine (10, 50, 100, 200, and 400 mu M) 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. 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 +/- A 14.6, 126.1 +/- A 24.5, and 402.7 +/- A 31.8 mu M, 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. 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. English SPRINGER JAPAN KK CENTRAL-NERVOUS-SYSTEM LOCAL-ANESTHETICS K+ CHANNEL TOXICITY BLOCK DETERMINANTS TANDEM The inhibitory effects of bupivacaine, levobupivacaine, and ropivacaine on K-2P (two-pore domain potassium) channel TREK-1 Article 10.1007/s00540-013-1661-1 1 JOURNAL OF ANESTHESIA, v.28, no.1, pp.81 - 86 JOURNAL OF ANESTHESIA 28 1 81 86 scie scopus 000331629300013 2-s2.0-84894414794 Anesthesiology Anesthesiology Article CENTRAL-NERVOUS-SYSTEM LOCAL-ANESTHETICS K+ CHANNEL TOXICITY BLOCK DETERMINANTS TANDEM Bupivacaine Levobupivacaine Ropivacaine TREK-1 Two-pore domain potassium channel