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

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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.

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Acknowledgments

This work was supported by the World Class Institute (WCI 2009-003) and MRC (2012-0000305) Programs of the NRF funded by the MEST of Korea.

Conflict of interest

All authors declare no financial interests.

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Authors and Affiliations

  1. Department of Anesthesiology and Pain Medicine, College of Medicine, Korea University, Seoul, Korea

    Hye Won Shin, Jeong Seop Soh & Hee Zoo Kim

  2. Center for Neural Science and WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, Korea

    Jinpyo Hong, Dong Ho Woo, Eun Mi Hwang, Jae-Yong Park & C. Justin Lee

  3. Department of Biochemistry, School of Medicine, Chungnam National University, Daejeon, Korea

    Jun Young Heo

  4. Department of Physiology, School of Medicine, Institute of Health Sciences, Gyeongsang University, Jinju, Korea

    Jae-Yong Park

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  1. Hye Won Shin
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Correspondence to Hye Won Shin or C. Justin Lee.

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Shin, H.W., Soh, J.S., Kim, H.Z. et al. The inhibitory effects of bupivacaine, levobupivacaine, and ropivacaine on K2P (two-pore domain potassium) channel TREK-1. J Anesth 28, 81–86 (2014). https://doi.org/10.1007/s00540-013-1661-1

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  • DOI: https://doi.org/10.1007/s00540-013-1661-1

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