Single-Walled Carbon Nanotubes Inhibit TRPC4-Mediated Muscarinic Cation Current in Mouse Ileal Myocytes.
Single-Walled Carbon Nanotubes Inhibit TRPC4-Mediated Muscarinic Cation Current in Mouse Ileal Myocytes.
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单壁碳纳米管抑制小鼠回肠肌细胞中TRPC 4介导的毒蕈碱阳离子电流。
DOI：
10.3390/nano11123410
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发表时间：
2021-12-16
期刊：
影响因子：
--
通讯作者：
Zholos AV
中科院分区：
文献类型：
--
作者：
Al Kury LT;Papandreou D;Hurmach VV;Dryn DO;Melnyk MI;Platonov MO;Prylutskyy YI;Ritter U;Scharff P;Zholos AV
单壁碳纳米管(SWCNTs)具有独特的物理和化学性质，是一种具有生物相容性的纳米结构材料，在生物医学领域具有广泛的应用前景。单壁碳纳米管不是药物分子的惰性载体，因为它们可以与包括离子通道在内的各种生物大分子相互作用。为探讨单壁碳纳米管抑制细胞内γS(200μM)诱发的M受体阳离子电流的作用机制，我们采用全细胞膜片钳方法。在这里，我们使用分子对接/分子动力学模拟和全细胞电流的直接膜片钳记录显示，在含有直径0.5-1.5 nm的单个SWCNTs的水悬浮液中，通过羧化纯化和功能化的SWCNTs可以抑制主要由回肠平滑肌细胞中的TRPC4阳离子通道携带的mICAT，并且是小肠胆碱能兴奋-收缩偶联的主要调节因子。这种抑制是不依赖于电压的，并且与缩短通道的平均开放时间有关。这些结果表明，单壁碳纳米管直接阻断了TRPC4通道，可能代表了一类新的TRPC4调节剂。
Single-walled carbon nanotubes (SWCNTs) are characterized by a combination of rather unique physical and chemical properties, which makes them interesting biocompatible nanostructured materials for various applications, including in the biomedical field. SWCNTs are not inert carriers of drug molecules, as they may interact with various biological macromolecules, including ion channels. To investigate the mechanisms of the inhibitory effects of SWCNTs on the muscarinic receptor cation current (mICAT), induced by intracellular GTPγs (200 μM), in isolated mouse ileal myocytes, we have used the patch-clamp method in the whole-cell configuration. Here, we use molecular docking/molecular dynamics simulations and direct patch-clamp recordings of whole-cell currents to show that SWCNTs, purified and functionalized by carboxylation in water suspension containing single SWCNTs with a diameter of 0.5–1.5 nm, can inhibit mICAT, which is mainly carried by TRPC4 cation channels in ileal smooth muscle cells, and is the main regulator of cholinergic excitation–contraction coupling in the small intestinal tract. This inhibition was voltage-independent and associated with a shortening of the mean open time of the channel. These results suggest that SWCNTs cause a direct blockage of the TRPC4 channel and may represent a novel class of TRPC4 modulators.
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