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Increased transient receptor potential vanilloid type 1 (TRPV1) signaling in idiopathic overactive bladder urothelial cells
Author(s) -
Li Mingkai,
Sun Yan,
Simard J. Marc,
Chai Toby C.
Publication year - 2011
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.21045
Subject(s) - overactive bladder , trpv1 , transient receptor potential channel , medicine , receptor , endocrinology , western blot , urology , urothelial cell , intracellular , urinary bladder , urothelium , pathology , chemistry , biochemistry , alternative medicine , gene
Aims To measure transient receptor potential vanilloid type 1 (TRPV1) signaling in human bladder urothelial cells (BUC) from non‐neurogenic overactive bladder (OAB) patients and control subjects (NB) BUC. Materials and Methods Primary BUC cell cultures were derived from cystoscopic biopsies from two OAB and two NB subjects. TRPV1 expression was detected by immunofluorescence, PCR and Western blot staining. TRPV1 function was assessed by capsaicin (CAP, 6 µM)‐evoked intracellular calcium ([Ca 2+ ] i ) changes measured by microfluorimetry imaging. CAP evoked changes in inward and outward currents were recorded electrophysiologically using excised outside‐out patches and whole cell configurations using various protocols. Results OAB BUC had significantly increased expression of TRPV1 compared to NB BUC on Western blot. CAP evoked significantly higher maximal [Ca 2+ ] i change over baseline in OAB (84.71 ± 8.96%) compared to NB BUC (60.32 ± 7.93%) ( P < 0.05). CAP induced significantly greater percent change in single channel open probability (205.94 ± 20.53% OAB vs. 141.26 ± 16.53% NB, P < 0.05) and normalized inward currents (13.54 ± 1.6 4 pA/pF OAB vs. 8.28 ± 0.89 pA/pF NB, P < 0.05). CAP caused significantly higher percent increase from baseline of whole cell outward currents in OAB (177.12 ± 44.46%) compared to NB BUC (135.98 ± 44.28%) ( P < 0.05). Similarly thermal stimulus (45°C solution) evoked significantly higher percent increase in whole cell outward currents in OAB (183.93 ± 14.07%) compared to NB (145.61 ± 10.12%) BUC ( P < 0.05). These responses were blocked by 10 µM capsazepine (CPZ), a TRPV1 antagonist. Conclusions Because only a few subjects were studied, augmented TRPV1 signaling cannot be generalized to all OAB subjects. However, the findings are consistent with the hypothesis that BUC are involved in sensory signaling. 30:606–611, 2011. © 2011 Wiley‐Liss, Inc.