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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Membrane potential differences and GABAA receptor expression in hepatic tumor and non-tumor stem cells
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Membrane potential differences and GABAA receptor expression in hepatic tumor and non-tumor stem cells

机译:肝肿瘤和非肿瘤干细胞的膜电位差异和GABAA受体表达

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摘要

The ability to differentiate tumor initiating stem cells (TISCs) from healthy, normal stem cells (NSCs) could have important diagnostic and therapeutic implications for patients with hepatocellular carcinoma (HCC). The aim of this study was to document and compare cell membrane potentials (PDs) and GABAA receptor subunit expression in hepatic TISCs and NSCs. PD values were determined in CD133+ Huh-7 TISCs and CD133+ WBF344 NSCs by single channel microelectrode impalement. GABAA receptor subunit expression was documented using immunohistochemistry (IH) in both cell lines as well as surgically resected HCC and healthy liver tissues. TISCs were significantly depolarized compared with NSCs (-4.0 ± 1.8 versus -11.0 ± 2.4 mV, respectively; p 0.05). GABAA α6 subunit expression was either absent or markedly attenuated, while γ3 subunit expression was abundant in TISCs and HCC compared with NSCs and healthy liver tissues. Exposure to the GABAA receptor agonist muscimol caused hyperpolarization of TISCs (Δ -4.4 ± 1.1) but depolarization of NSCs (Δ + 5.2 ± 2.3) and attenuation of TISC proliferative activity. We conclude that TISCs and NSCs have significantly different cell membrane potentials and these differences are associated with differences in GABAA receptor subunit expression.
机译:从健康的正常干细胞(NSC)中区分肿瘤起始干细胞(TISC)的能力可能对肝细胞癌(HCC)患者具有重要的诊断和治疗意义。这项研究的目的是记录和比较肝TISCs和NSCs中的细胞膜电位(PDs)和GABAA受体亚基表达。通过单通道微电极穿刺确定CD133 + Huh-7 TISC和CD133 + WBF344 NSC中的PD值。 GABAA受体亚基的表达已使用免疫组织化学(IH)在这两种细胞系以及手术切除的HCC和健康肝组织中进行了记录。与NSC相比,TISC显着去极化(分别为-4.0±1.8和-11.0±2.4 mV; p <0.05)。与NSC和健康肝组织相比,TISCs和HCC中GABAAα6亚基表达缺失或显着减弱,而γ3亚基表达丰富。暴露于GABAA受体激动剂麝香酚会引起TISC的超极化(Δ-4.4±1.1),但会导致NSC的去极化(Δ+ 5.2±2.3)和TISC增殖活性减弱。我们得出结论,TISC和NSC具有明显不同的细胞膜电位,这些差异与GABAA受体亚基表达的差异有关。

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