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Increased Efficacy and Potency Of Carbachol In Inducing Increases In Intracellular Calcium ([Ca2+]i) In Overactive Bladder (OAB) and Interstitial Cystitis (IC) Bladder Urothelial Cells (BUC)
Gopal Gupta*1, Shao-Gang Lu*2, Yan Sun*1, Michael Gold*2, Toby C Chai1
1University of Maryland School of Medicine, Baltimore, MD;2University of Maryland Dental School, Baltimore, MD
Introduction: BUC may play a role in the pathogenesis in bladder hypersensory conditions. Carbachol increases outward potassium current in IC BUC via BK-channel (Ca2+-activated potassium channel) suggesting increases in [Ca2+]i mediate this response.
Methods: BUC from 1 OAB, 4 controls and 4 IC were used. [Ca2+]i was measured with fura-2 ratiometric microfluorimetry. Carbachol-induced increases in [Ca2+]i were analyzed as a percent increase in fura-2 ratio. Dose-response curves were fitted with a modified Hill equation to obtain maximum effect (efficacy) and EC50 (potency).
Results: Carbachol's efficacy was significantly greater in IC compared to normal BUC (135.9% ± 7.5% vs. 91.8% ± 11.8%, p <0.05, see Figure). Its potency on IC BUC was significantly increased (1.1 ± 0.2 μM for IC vs. 3.4 ± 0.9 μM for normal BUC, p < 0.05). Because only 1 OAB patient was studied, no statistics could be performed; however, values in OAB fell between IC and normal BUC (OAB efficacy was 109.7% and potency was 1.5 μM).
Conclusions: This is the first report of carbachol induced changes in [Ca2+]i in BUC. IC BUC were the most sensitive to carbachol, followed by OAB BUC, then normal BUC. BUC may be an appropriate target for treating bladder hypersensory conditions. 
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