细胞内酸性阻碍了Riluzole和SKA-31的KCa3.1激活
Marco Cozzolino1, Gyorgy Panyi1
1Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Frontiers in pharmacology
|April 19, 2024
概括
在T细胞中的细胞内酸性损害KCa3.1激活剂的功效,可能限制癌症免疫疗法. 细胞外pH值不会影响KCa3.1电流或调节器的有效性.
科学领域:
- 离子通道生理学 离子通道生理学
- 癌症免疫学 癌症免疫学
- 细胞微环境是细胞微环境.
背景情况:
- 瘤微环境抑制了抗瘤免疫反应.
- 激活KCa3.1通道是一种增强抗瘤免疫力的策略.
- 瘤的酸度是微环境的一个关键特征.
研究的目的:
- 研究pH对KCa3.1电流的影响.
- 评估KCa3.1调节器Riluzole和SKA-31的pH敏感性.
主要方法:
- 全细胞补丁电生理学.
- 使用了人类淋巴细胞和感染的CHO细胞.
- 检查了野生类型和突变KCa3.1通道.
主要成果:
- KCa3.1 电流对细胞外pH (6.0-8.0) 的敏感性很小.
- 里卢和SKA-31的疗效不受细胞外pH的影响.
- 细胞内酸性酶导致缓慢,不可逆转的激活剂功效的损失.
结论:
- 在生理范围内,KCa3.1电流通常不敏感于pH值.
- 细胞内酸性增生可能会降低基于KCa3.1的癌症疗法的有效性.
- 需要进一步研究分子机制和体内相关性.
相关概念视频
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.2K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.2K
Electron Transport Chain: Complex I and II
13.1K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
13.1K
The Electron Transport Chain
16.7K
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
16.7K
Antiepileptic Drugs: Potassium Channel Activators
176
Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...
Ezogabine has gained approval as an adjunctive treatment...
176


