Poster, Podium & Video Sessions
Presentation Authors: Ken Lee*, Tomoko Maki, Ryosuke Takahashi, Masatoshi Eto, Shunichi Kajioka, Fukuoka, Japan
Introduction: We have reported the novel mechanism which is sensitive to extracellular calcium concentration ([Ca2+]out) co-related with the force development of contraction in human and pig urethral smooth muscle (USM). In addtion to this mechanism, the present study first revealed the distinctive temperature sensitivity of the tension force development of USM. Focusing on this temperature sensitivity of USM, the contribution of TRPV (Transient receptor potential vanilloid) channel was investigated.
Methods: The procedures described have been approved by ethical committee at Kyushu University hospital. Human USM was obtained from patients with bladder cancer undertaken radical cystectomy, while pig one from local abattoir. Isolated intact USM were dissected. Responses to warming-induced contraction (WIC) corresponding to [Ca2+]out were investigated using isometric force recording. Various TRPV channel agonists and antagonists were examined.
Results: The graded extracellular temperature change from 10°C to 37°C increased a sustained contraction (4.1 ± 0.7g, N=6) in a temperature dependent manner in human and pig USM (fig, A,B & C) but not observed in detrusor. Extracellular Ca2+ free solution did not induce WIC. Contractility upon [Ca2+]out was variable to each temperature (fig, D). Even in the presence of tetrodotoxin (1 μM) and prazosin (1 μM), these responses were also reproducible. TRPV1 agonists, capsaicin (up to 1 mM) or resiniferatoxin (10 μM) and accordingly, a TRPV4 agonist, GSK1016790A (1 μM) failed to induce pig USM contraction. A TRPV channel family antagonist, Ruthenium Red (100 μM) never inhibited WIC.
Conclusions: Extracellular Ca2+ is essential for the generation of WIC, suggesting that the mechanism underlying WIC requires transmembrane Ca2+ entry or intracellular Ca2+ metabolic process. Though TRPV channel-related agents did not modulate USM contraction, it is strongly suggested that WIC results from TRPV channel activation. Subtype, splice-variant, or gene polymorphism of TRPV channel but not a typical one may be involved in WIC. This novel mechanism in urethra but not in detrusor might be a candidate for a treatment of lower urinary tract dysfunctions.
Source Of Funding: none
Ken Lee, PhD student (basic researcher), Department of Urology, Kyushu University, Japan
AUA abstract title: Is TRP channel involved in warming induced contraction of human and pig urethral smooth muscle?
Content: We have been focusing on the relation between urethral smooth muscle contraction and thermosensitivity, especially focusing on the participation of TRP channels. In the session, effects of several TRP channel modulators used are going to be discussed.
Saturday, May 13
3:30 PM – 5:30 PM