Functional analysis of a novel candidate molecule for a sodium level sensor of body fluids

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15334
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Nagoya City University
• Principal Investigator: Mariko Hoshikawa 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (30898060)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 体液恒常性維持機構

Outline of Final Research Achievements

The subfornical organ is involved in maintaining fluid balance by monitoring the sodium concentration of body fluids and controlling water and salt intake behaviours. We found that channel X is a constitutively open sodium channel that is expressed in excitatory neurons in the subfornical organ. In addition, the water intake behaviour of channel X knockout mice, in which the sodium concentration of body fluids increased due to acute water deprivation, was also reduced. These findings suggest that channel X may be a novel sodium level sensor of body fluids in the subfornical organ. The results of this study are expected to lead to an understanding of the mechanisms that maintain body fluid homeostasis and the mechanisms that cause hypertension.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

新規体液Na+センサー分子の同定による、体液恒常性維持機構の解明は、生命の根源に関わる極めて重要な研究課題である。体液Na+濃度の上昇は、血液の浸透圧活性を上げることで高血圧を導くが、その他、脳弓下器官→終板脈管器官（水分摂取行動）→延髄吻側腹外側野（交感神経活動の中枢）へと情報が伝えられ、交感神経系が刺激されることでも血圧上昇に働く。チャネルXの活性調整剤は、水分・塩分摂取行動と自律神経系の両者を制御する新しいタイプの高血圧治療薬になり得る。本研究は、体液恒常性の制御機構や高血圧の病態生理の解明に繋がるのみならず、そのような創薬の基盤となりうるものである。