TRPM5的激活取决于和PKC酸化的协同作用
1The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Karem, Jerusalem, 9112102, Israel.
蛋白激酶C (PKC) 酸化和细胞内的增加对于激活TRPM5通道至关重要. 这一发现为涉及TRPM5调制的疾病提供了新的治疗点.
科学领域:
- 离子通道生理学 离子通道生理学
- 分子药理学分子药理学
背景情况:
- 暂时受体潜力梅拉斯5 (TRPM5) 是一种激活的离子通道,对胰岛素分泌和味道至关重要.
- TRPM5激活与Gq/G蛋白合受体 (GPCRs) 和细胞内升高有关.
- 控制TRPM5激活的精确分子机制尚不完全理解.
研究的目的:
- 阐明TRPM5通道激活所需的分子决定因素.
- 研究细胞内和蛋白激酶C (PKC) 酸化在TRPM5功能中的作用.
主要方法:
- 在表达TRPM5.5的细胞中的电生理记录.
- 细胞内水平的药理学操纵.
- 评估PKC活动及其对TRPM5电流的影响.
主要成果:
- TRPM5通道的激活需要PKC酸化和高细胞内Ca2+水平.
- 在生理膜潜力下,PKC酸化对TRPM5电流至关重要.
- 仅仅的升高就只能在正电压下激活TRPM5.
结论:
- 协调的细胞内释放和PKC酸化对于TRPM5激活至关重要.
- 调节PKC活动为TRPM5相关疾病提供了潜在的治疗策略.
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