小檗碱对大鼠肝细胞离子通道的抑制作用。

Inhibitory effects of berberine on ion channels of rat hepatocytes.

作者信息

Wang Fang, Zhou Hong-Yi, Zhao Gang, Fu Li-Ying, Cheng Lan, Chen Jian-Guo, Yao Wei-Xing

机构信息

Department of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.

出版信息

World J Gastroenterol. 2004 Oct 1;10(19):2842-5. doi: 10.3748/wjg.v10.i19.2842.

DOI:10.3748/wjg.v10.i19.2842

PMID:15334682

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4572114/

Abstract

AIM

To examine the effects of berberine, an isoquinoline alkaloid with a long history used as a tonic remedy for liver and heart, on ion channels of isolated rat hepatocytes.

METHODS

Tight-seal whole-cell patch-clamp techniques were performed to investigate the effects of berberine on the delayed outward potassium currents (I(K)), inward rectifier potassium currents (I(K1)) and Ca(2+) release-activated Ca(2+) currents (I(CRAC)) in enzymatically isolated rat hepatocytes.

RESULTS

Berberine 1-300 micromol/L reduced I(K) in a concentration-dependent manner with EC(50) of 38.86+/-5.37 micromol/L and n(H) of 0.82+/-0.05 (n = 8). When the bath solution was changed to tetraethylammonium (TEA) 8 mmol/L, I(K) was inhibited. Berberine 30 micromol/L reduced I(K) at all examined membrane potentials, especially at potentials positive to +60 mV (n = 8, P<0.05 or P<0.01 vs control). Berberine had mild inhibitory effects on I(K1) in rat hepatocytes. Berberine 1-300 micromol/L also inhibited I(CRAC) in a concentration-dependent fashion. The fitting parameters were EC(50) = 47.20+/-10.86 micromol/L, n(H) = 0.71+/-0.09 (n = 8). The peak value of I(CRAC) in the I-V relationship was decreased by berberine 30 micromol/L at potential negative to -80 mV (n = 8, P<0.05 vs control). But the reverse potential of I(CRAC) occurred at voltage 0 mV in all cells.

CONCLUSION

Berberine has inhibitory effects on potassium and calcium currents in isolated rat hepatocytes, which may be involved in hepatoprotection.

摘要

目的

研究小檗碱（一种历史悠久的用于肝脏和心脏滋补治疗的异喹啉生物碱）对分离的大鼠肝细胞离子通道的影响。

方法

采用全细胞膜片钳技术，研究小檗碱对酶分离的大鼠肝细胞延迟外向钾电流（I(K)）、内向整流钾电流（I(K1)）和钙释放激活钙电流（I(CRAC)）的影响。

结果

1-300 μmol/L小檗碱以浓度依赖性方式降低I(K)，半数有效浓度（EC(50)）为38.86±5.37 μmol/L，Hill系数（n(H)）为0.82±0.05（n = 8）。当浴液更换为8 mmol/L四乙铵（TEA）时，I(K)受到抑制。30 μmol/L小檗碱在所有检测的膜电位下均降低I(K)，尤其是在膜电位高于+60 mV时（n = 8，与对照组相比P<0.05或P<0.01）。小檗碱对大鼠肝细胞的I(K1)有轻度抑制作用。1-300 μmol/L小檗碱也以浓度依赖性方式抑制I(CRAC)。拟合参数为EC(50) = 47.20±10.86 μmol/L，n(H) = 0.71±0.09（n = 8）。在膜电位低于-80 mV时，30 μmol/L小檗碱使I(CRAC)的电流-电压关系（I-V关系）峰值降低（n = 8，与对照组相比P<0.05）。但所有细胞中I(CRAC)的反转电位均出现在0 mV电压处。