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

Hye Won Shin, Jeong Seop Soh, Hee Zoo Kim, Jinpyo Hong, Dong Ho Woo, Jun Young Heo, Eun Mi Hwang, Jae Yong Park, C. Justin 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

Keywords

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

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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