Abstract:
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.
journal_name
Neurourol Urodynjournal_title
Neurourology and urodynamicsauthors
Li M,Sun Y,Simard JM,Chai TCdoi
10.1002/nau.21045subject
Has Abstractpub_date
2011-04-01 00:00:00pages
606-11issue
4eissn
0733-2467issn
1520-6777journal_volume
30pub_type
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