Is underactive bladder really downregulation of bladder contractility?

2016 Fiscal Year Final Research Report

• Project/Area Number: 26670705
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: HASHITANI HIkaru 名古屋市立大学, 大学院医学研究科, 教授 (10315905)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 低活動膀胱 / 平滑筋 / 粘膜筋板 / 副甲状腺ホルモン関連ペプチド / TRPV4チャネル / 血小板由来成長因子α受容体 / SK３チャネル

Outline of Final Research Achievements

Role of intrinsic relaxation mechanisms of the bladder in regulating spontaneous contractility was investigated in smooth muscles of detrusor and muscularis mucosae. PTHrP, an endogenous muscle relaxant released from detrusor upon bladder wall distension, had a more pronounced inhibitory effects on spontaneous contractions of detrusor than those of muscularis mucosae. TRPV4, a Ca2+-permeable stretch-activated cation channels expressed in both detrusor and muscularis mucosae. Ca2+ influx through TRPV4 appears to activate BK channels to suppress spontaneous contractions, and thus a functional coupling of TRPV4 with BK channels may act as a self-limiting mechanism for bladder contractility. SK channel openers prolonged the after-hyperpolarization in both detrusor and muscularis mucosae, indicating the SK channels expression in not only PDGFRα (+) cells but also detrusor. Upregulation of these intrinsic relaxation mechanisms may result in underactive bladder.

Free Research Field

平滑筋生理学