Login to Access Video or Poster Abstract: MP42-19
Sources of Funding: none

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.

Funding

none