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首页> 外文期刊>American Journal of Physiology >Effects of the gap junction blocker glycyrrhetinic acid on gastrointestinal smooth muscle cells.
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Effects of the gap junction blocker glycyrrhetinic acid on gastrointestinal smooth muscle cells.

机译：间隙连接阻滞剂甘草次酸对胃肠道平滑肌细胞的影响。

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摘要

In the tunica muscularis of the gastrointestinal (GI) tract, gap junctions form low-resistance pathways between pacemaker cells known as interstitial cells of Cajal (ICCs) and between ICC and smooth muscle cells. Coupling via these junctions facilitates electrical slow-wave propagation and responses of smooth muscle to enteric motor nerves. Glycyrrhetinic acid (GA) has been shown to uncouple gap junctions, but previous studies have shown apparent nonspecific effects of GA in a variety of tissues. We tested the effects of GA using isometric force measurements, intracellular microelectrode recordings, the patch-clamp technique, and the spread of Lucifer yellow within cultured ICC networks. In murine small intestinal muscles, beta-GA (10 muM) decreased phasic contractions and depolarized resting membrane potential. Preincubation of GA inhibited the spread of Lucifer yellow, increased input resistance, and decreased cell capacitance in ICC networks, suggesting that GA uncoupled ICCs. In patch-clamp experiments of isolated jejunal myocytes, GA significantly decreased L-type Ca(2+) current in a dose-dependent manner without affecting the voltage dependence of this current. The IC(50) for Ca(2+) currents was 1.9 muM, which is lower than the concentrations used to block gap junctions. GA also significantly increased large-conductance Ca(2+)-activated K(+) currents but decreased net delayed rectifier K(+) currents, including 4-aminopyridine and tetraethylammonium-resistant currents. In conclusion, the reduction of phasic contractile activity of GI muscles by GA is likely a consequence of its inhibitory effects on gap junctions and voltage-dependent Ca(2+) currents. Membrane depolarization may be a consequence of uncoupling effects of GA on gap junctions between ICCs and smooth muscles and inhibition of K(+) conductances in smooth muscle cells.
机译：在胃肠道（GI）的肌膜中，间隙连接在称为Cajal间质细胞（ICC）的起搏器细胞之间，ICC与平滑肌细胞之间形成低电阻途径。通过这些连接点的耦合有助于电慢波传播以及平滑肌对肠运动神经的反应。甘草次酸（GA）已被证明能解离缝隙连接，但先前的研究表明GA在多种组织中具有明显的非特异性作用。我们使用等距力测量，细胞内微电极记录，膜片钳技术以及路西法黄在培养的ICC网络中的扩散来测试GA的效果。在鼠小肠肌肉中，β-GA（10μM）减少了相收缩和静息膜电位去极化。 GA的预孵育抑制了ICC网络中路西法黄的扩散，输入电阻的增加和细胞电容的降低，这表明GA可以使ICC脱钩。在隔离空肠肌细胞的膜片钳实验中，GA以剂量依赖性方式显着降低L型Ca（2+）电流，而不会影响该电流的电压依赖性。 Ca（2+）电流的IC（50）为1.9μM，低于用于阻挡间隙连接的浓度。 GA还显着增加了大电导Ca（2+）激活的K（+）电流，但降低了净延迟整流K（+）电流，包括4-氨基吡啶和四乙铵抗性电流。总之，GA减少GI肌肉的阶段性收缩活动可能是其对间隙连接和电压依赖性Ca（2+）电流的抑制作用的结果。膜去极化可能是GA对ICC与平滑肌之间的间隙连接的解偶联作用以及对平滑肌细胞中K（+）电导的抑制作用的结果。

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