Effects of pericyte-specific ATP-dependent potassium channel on cardiac function

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23835
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0802:Biomedical structure and function and related fields
• Research Institution: Nippon Medical School
• Principal Investigator: Ando Koji 日本医科大学, 先端医学研究所, 講師 (10736010)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: ペリサイト / Kcnj8 / Abcc9

Outline of Final Research Achievements

In this study, we found that the K-ATP channel functions with the onset of ABCC9/KCNJ8 expression in the pericytes from the early developmental stage. While inhibition of K-ATP channel was converted to the elevation of intracellular Ca2 +, transient activation of the K-ATP channel in the resting condition unexpectedly caused little Ca2 + changes. Using the experimental model developed in this study, we are now able to analyze Ca2 + kinetics and gene expression changes in the Kcnj8 or Abcc9 mutants, and analyze the association between pericyte intracellular Ca2 + fluctuations and heart disease. On the other hand, we found the change in Kcnj8 gene expression along the development in the mouse heart. In the early developmental mouse heart, Kcnj8 was also expressed in epicardial cells, implying the possibility of a new mechanism other than the hypothesis that pericyte abnormalities that were initially predicted cause heart disease.

Free Research Field

血管生物学

Academic Significance and Societal Importance of the Research Achievements

心疾患は死因の主要な原因であることから、心臓におけるペリサイト機能解析は学術的側面に加え、臨床面でも重要な課題の一つであると言える。ペリサイト特異的ATP依存性カリウムチャネル異常が心疾患を誘発するメカニズムは十分には分かっておらず、本研究によりKcnj8遺伝子の発現変化とペリサイトにおけるK-ATPチャネルと細胞内Ca2+濃度の連関を明らかに出来たことは、今後の詳細なK-ATPチャネルの役割およびその異常により誘発される心疾患の発症機構の理解に貢献するものと考えられる。