Online

Shields, Ryan Thomas

Pharmacology

2022

M.S.

Detrusor muscle overactivity in the bladder wall is the hallmark symptom of overactive bladder syndrome and the principal target of therapy that seeks to reduce incontinence and urinary urgency. However, these interventions typically fail to alleviate long-term detrusor overactivity and simply mask the underlying pathology while also potentially introducing undesirable side effects that disrupt quality of life. One alternative mechanism driving of overactive bladder is attributed to ischemia within the bladder, which is subject to enormous swings in pressure and tension on its vasculature restricting blood flow. This observation, coupled with the fact that healthy vascular tissue within the bladder lacks a myogenic response to increasing intraluminal pressures, provides a potential pathological explanation and new therapeutic targets for managing overactive bladder. We evaluated whether conscious voiding behavior in mice is impacted with the introduction of myogenic tone into the bladder vasculature via knock out of the inward-rectifier potassium channel, KIR2.1. The voiding activity of 10 smooth muscle-specific tamoxifen-inducible KIR2.1 knockout mice were observed pre- and post-tamoxifen treatment using the UroVoid System: a novel apparatus for measuring micturition events in real time. A consistent difference of voiding behavior between knockout and control treatment groups could not be demonstrated. However, voiding frequency of all mice within the trials are elevated above established literature values as well as prior trials of different mice within the UroVoid. Absent controls and potential confounding factors from the environment in which the trials take place obscured a definitive conclusion from the data while emphasizing the importance of comprehensive environmental vetting and strict protocol adherence prior to conducting UroVoid experiments. Thus, future experiments can still effectively test the role of KIR2.1 channels in bladder health as long as the confounding factors are accounted for.