細胞内カリウム濃度低下による神経細胞保護効果の可能性

• Published in: 日本薬理学会年会要旨集 p. 2-O-B1-4
• Main Authors: 林, 亮佑, 金城, 俊彦, 倉本, 展行, 宇野, 恭介
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2021
• Subjects: degeneration; depolarization; ion channel; mitochondria
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.94.0_2-O-B1-4

Intracellular (cytosolic) potassium ion concentration is higher than extracellular space, since it is regulated by transport proteins on cell membranes such as sodium pumps. Therefore, potassium channel opening on the cell membrane lowers the intracellular potassium ion concentration by allowing potassium to flow out of the cell. On the other hand, the potassium concentration in the mitochondrial matrix is ​​lower than that in the cytosol. Therefore, the mitochondrial membrane permeable transition pore (PTP) opening of the inner mitochondrial membrane flows into the potassium matrix and depolarizes the inner membrane. Excessive depolarization of the inner membrane induces cell death. Therefore, in this study, we investigated the possibility that the decrease in intracellular potassium concentration suppresses cell death caused by mitochondrial depolarization. NMDA exposure to primary cortical neurons induced mitochondrial depolarization and neuronal cell death with increased intracellular calcium concentration, which was suppressed by pretreatment of GABAB receptor agonists. The neuronal cell death inhibitory effect of GABAB receptor agonists was suppressed by the G protein-activating potassium channel inhibitor tertiapin, not by the adenylate cyclase activator forskolin. In addition, the ATP-sensitive potassium channel opener minoxidil significantly reduced intracellular potassium levels and suppressed mitochondrial depolarization and neuronal cell death associated with NMDA exposure. From the above, it is suggested that reducing the intracellular potassium level suppresses neuronal cell death mediated by mitochondrial depolarization due to excitatory stimulation.