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布比卡因抑制人胚肾 293 细胞中小电导钙激活钾通道 2 型。

Bupivacaine inhibits a small conductance calcium-activated potassium type 2 channel in human embryonic kidney 293 cells.

机构信息

Department of Pain Management, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 324 Jingwu Road, 250021, Jinan, China.

Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China.

出版信息

BMC Pharmacol Toxicol. 2021 Mar 12;22(1):15. doi: 10.1186/s40360-021-00481-2.

DOI:10.1186/s40360-021-00481-2
PMID:33712065
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7953788/
Abstract

BACKGROUND

Bupivacaine blocks many ion channels in the heart muscle, causing severe cardiotoxicity. Small-conductance calcium-activated potassium type 2 channels (SK2 channels) are widely distributed in the heart cells and are involved in relevant physiological functions. However, whether bupivacaine can inhibit SK2 channels is still unclear. This study investigated the effect of bupivacaine on SK2 channels.

METHODS

The SK2 channel gene was transfected into human embryonic kidney 293 cells (HEK-293 cells) with Lipofectamine 2000. The whole-cell patch-clamp technique was used to examine the effect of bupivacaine on SK2 channels. The concentration-response relationship of bupivacaine for inhibiting SK2 currents (0 mV) was fitted to a Hill equation, and the half-maximal inhibitory concentration (IC50) value was determined.

RESULTS

Bupivacaine inhibited the SK2 channels reversibly in a dose-dependent manner. The IC50 value of bupivacaine, ropivacaine, and lidocaine on SK2 currents was 16.5, 46.5, and 77.8µM, respectively. The degree of SK2 current inhibition by bupivacaine depended on the intracellular concentration of free calcium.

CONCLUSIONS

The results of this study suggested the inhibitory effect of bupivacaine on SK2 channels. Future studies should explore the effects of SK2 on bupivacaine cardiotoxicity.

摘要

背景

布比卡因会阻断心肌中的多种离子通道，从而导致严重的心脏毒性。小电导钙激活钾 2 型通道（SK2 通道）广泛分布于心脏细胞中，参与相关的生理功能。然而，布比卡因是否能抑制 SK2 通道仍不清楚。本研究旨在探讨布比卡因对 SK2 通道的影响。

方法

采用 Lipofectamine 2000 将 SK2 通道基因转染入人胚肾 293 细胞（HEK-293 细胞）。采用全细胞膜片钳技术检测布比卡因对 SK2 通道的作用。采用 Hill 方程拟合布比卡因抑制 SK2 电流（0 mV）的浓度-反应关系，计算半抑制浓度（IC50）值。

结果

布比卡因呈浓度依赖性、可逆性抑制 SK2 通道。布比卡因、罗哌卡因和利多卡因对 SK2 电流的半数抑制浓度（IC50）值分别为 16.5、46.5 和 77.8µM。布比卡因对 SK2 电流的抑制程度取决于细胞内游离钙浓度。

结论

本研究结果提示布比卡因对 SK2 通道具有抑制作用。未来的研究应探讨 SK2 对布比卡因心脏毒性的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d21/7953788/eab323157760/40360_2021_481_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d21/7953788/e4de2279a8d9/40360_2021_481_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d21/7953788/cc8b2a275129/40360_2021_481_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d21/7953788/eab323157760/40360_2021_481_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d21/7953788/e4de2279a8d9/40360_2021_481_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d21/7953788/cc8b2a275129/40360_2021_481_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d21/7953788/eab323157760/40360_2021_481_Fig3_HTML.jpg

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