作为质子激活化通道内源抑制剂的弱酸
Inês C A Pombeiro Stein1,2, Maren Schulz1, Daniel Rudolf1
1Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Cells
|July 25, 2025
概括
弱酸通过一个独特的细胞外结合部位抑制质子激活化物 (PAC) 通道,涉及氨酸93. 这一发现为内源性弱酸对PAC通道调节提供了新的见解.
科学领域:
- 身体生理学 身体生理学
- 分子生物学分子生物学
- 道病变是一种通道病变.
背景情况:
- 质子激活化物 (PAC) 通道被广泛表达,在对质子度敏感的生理和病理生理过程中发挥作用.
- 强酸通过细胞外质子结合点激活了PAC通道.
研究的目的:
- 研究弱酸抑制PAC通道的机制.
- 确定特定的结合部位和分子决定因素,参与PAC通道的弱酸抑制.
主要方法:
- 在HEK293T细胞,表达人类PAC突变体的PAC-knockout细胞和hiPSC衍生的心肌细胞上进行全细胞补丁电生理学.
- 在HEK293T细胞中检查质子诱导的细胞毒性.
- 在hPAC中的细胞外阿基尼93残留物的局部定向突变发生.
主要成果:
- 弱酸,包括酸,乳酸,酸,伊塔康酸和β-基酸,可逆地抑制内源性和重组性PAC通道,以度和pH值依赖的方式.
- 将细胞外的氨酸93转化为氨酸 (hPAC-Arg93Ala) 显著降低了某些弱酸的抑制作用,例如氨酸.
- 乳酸抑制了PAC通道,但没有影响HEK293细胞中质子诱导的细胞毒性.
结论:
- 弱酸通过一种独特的细胞外机制抑制PAC通道,其中包括氨酸93.
- 这些发现突出了内源性弱酸对PAC通道的新调节途径,这表明了各种生物环境中的潜在影响.
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