血管平滑肌细胞中tmem16a介导的Ca2+激活Cl -电流的微管依赖性调节

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences Pub Date : 2025-09-06 DOI:10.1016/j.jphs.2025.09.001

Ryosuke Hemmi , Akane Suzukawa , Moe Fujiwara , Rubii Kondo , Yoshiaki Suzuki , Aya Yamamura , Hisao Yamamura

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引用次数: 0

摘要

TMEM16A通道介导血管平滑肌细胞（VSMCs）中Ca2+激活的Cl - (ClCa)电流，其活性受细胞骨架动力学的影响。本研究探讨了微管在TMEM16A调控中的功能作用。微管聚合抑制剂、秋水仙碱和诺可达唑可降低TMEM16A蛋白的质膜定位和TMEM16A介导的ClCa电流。在表达tmem16a的HEK293细胞中也观察到类似的效果，秋水仙碱的IC50值为3.0 μM，诺可唑的IC50值为0.6 μM。急性应用无明显效果。这些发现表明，微管是维持vsmc中TMEM16A通道表达和功能活性所必需的。

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Microtubule-dependent regulation of TMEM16A-mediated Ca2+-activated Cl− currents in vascular smooth muscle cells

TMEM16A channels mediate Ca²⁺-activated Cl⁻ (Cl_Ca) currents in vascular smooth muscle cells (VSMCs), and their activity is influenced by cytoskeletal dynamics. The present study examined the functional role of microtubules in TMEM16A regulation. Treatment with microtubule polymerization inhibitors, colchicine and nocodazole, reduced plasma membrane localization of TMEM16A protein and TMEM16A-mediated Cl_Ca currents. Similar effects were observed in TMEM16A-expressing HEK293 cells, with IC₅₀ values of 3.0 μM for colchicine and 0.6 μM for nocodazole. In contrast, acute application had no significant effect. These findings indicate that microtubules are required for maintaining the expression and functional activity of TMEM16A channels in VSMCs.

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来源期刊

Journal of pharmacological sciences 医学-药学

CiteScore

6.20

自引率

2.90%

发文量

104

审稿时长

31 days

期刊介绍： Journal of Pharmacological Sciences (JPS) is an international open access journal intended for the advancement of pharmacological sciences in the world. The Journal welcomes submissions in all fields of experimental and clinical pharmacology, including neuroscience, and biochemical, cellular, and molecular pharmacology for publication as Reviews, Full Papers or Short Communications. Short Communications are short research article intended to provide novel and exciting pharmacological findings. Manuscripts concerning descriptive case reports, pharmacokinetic and pharmacodynamic studies without pharmacological mechanism and dose-response determinations are not acceptable and will be rejected without peer review. The ethnopharmacological studies are also out of the scope of this journal. Furthermore, JPS does not publish work on the actions of biological extracts unknown chemical composition.