Elucidation of the Molecular Mechanism underlying the Sphingolipid-Mediated Regulation of Potassium Channel Function

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590319
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Osaka University
• Principal Investigator: FURUTANI Kazuharu 大阪大学, 医学(系)研究科(研究院), 助教 (40452437)
• Co-Investigator(Renkei-kenkyūsha): KURACHI Yoshihisa 大阪大学, 大学院医学系研究科, 教授 (30142011)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 生理活性脂質 / イオンチャネル / 生理学 / 薬理学 / 細胞内シグナル伝達

Outline of Final Research Achievements

Sphingolipids, a class of lipids, are components of lipid bilayer of biological membranes. Membrane sphingolipids serve as a reservoir for bioactive metabolites including ceramide (Cer), sphingosine (Sph) and sphingosine-1-phosphate. In this study, we examined if functions of inwardly rectifying potassium (Kir) channels are controlled by sphingolipids. Kir channels were expressed in cultured mammalian cells or Xenopus oocytes, and electrophyiological analyses were performed. We found that intracellular Sph inhibits Kir currents. Normally, the most abundant sphingolipids in the cell is the plasma membrane sphingomyelin (SM), and Sph is biosynthesized from SM via Cer. In response to the hydrolysis of SM by sphingomyelinase (SMase), Kir channel currents slowly decrease. The SMase-induced current decreases were suppressed by pharmacological inhibitions of the Sph biosynthetic pathway. These results suggest that endogenous sphingolipids inhibit Kir channels via Sph.

Free Research Field

薬理学