Effect of Muscarinic Agonists on Outward Current in Bladder Urothelial Cells

Mara R Holton, P. Sean Van Zijl, Mingkui Chen*, Yan Sun, J. Marc Simard*, Toby C Chai
University of Maryland, Baltimore, MD

Introduction:
Traditionally, the action of anti-muscarinics is thought to occur on the detrusor smooth muscle in quelling detrusor overactivity (DO). However, the action of anti-muscarinics may also occur at the BUC. Our objective is to determine whether M2 receptors exist on BUC and whether they are functionally active.
Methods:
Human BUC were electrophysiologically studied with and without exposure to carbachol. Molecular analysis of BUC utilizing RT-PCR, and Western blotting was undertaken to assesss the expression of M2 receptors.
Results:
The baseline outward current is depicted in the figure, tracing a. The addition of 0.5mM carbachol to BUC resulted in an increased owtward current (tracing b). This increased current is at least partially mediated by Ca-activated potassium channel (BK) as 100nM iberiotoxin (a specific BK channel antagonist) reduced the current (tracing c). RT-PCR and Western blots confirmed expression of M2 subtype in human BUC.
Conclusions:
Carbachol increased the outward current of BUC. The partial normalization of the outward current with iberiotoxin suggest that a portion of the outward current is mediated by the BK channel. The action of anti-muscarinics in treatment of voiding dysfunction could work at the level of the urothelium, in addition to the detrusor smooth muscle.

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