The goal of this P20 project is to establish the Developmental Center for Human Urinary Bladder Myogenic Mechanisms by Ion Channels in Health and Disease (DC-HUB) focused on the role of smooth muscle ion channels in overactive bladder (OAB) etiology and related detrusor overactivity (DO). The DC-HUB Center will be based at the University of Tennessee Health Science Center (UTHSC) and involves the Colleges of Pharmacy and Medicine. The proposed studies will benefit from the robust clinical and basic science environments of the UTHSC campus. UTHSC has many established biomedical sciences investigators and an excellent urology team. Georgi V. Petkov, PhD, an established investigator with multidisciplinary training in biochemistry, physiology, pharmacology, electrophysiology, and urological research will serve as the DC-HUB Center Director and Principal Investigator. A major strength of our strategic program on ion channel research that puts us at the forefront of basic urological research is our conduct of this research in collaboration with an impressive cadre of clinical scientists including 11 faculty members and 15 MD urology residents. Robert Wake, MD, an established UTHSC clinical urologist, will coordinate the urology team effort. The collaboration will be supported by Eric Rovner, MD, an internationally renowned OAB urology expert and his clinical team based at the Medical University of South Carolina (MUSC), consisting of 7 faculty members and 15 MD urology residents. Voltage- gated potassium ion (KV) channels and transient receptor potential (TRP) channels are expressed in the urinary bladder. Our central hypothesis is that KV and TRP channels are key regulators of urinary bladder physiology, and therefore, changes in their expression, function, or regulation may lead to DO/OAB. Our team can regularly make use of donor bladder specimens to study KV and TRP channel function in humans and correlate basic science findings with patient clinical profiles. We will use bladder tissues both from patients without an OAB clinical history (controls) and from subjects with OAB or urodynamically proven DO (idiopathic or neurogenic) as well as experimental animals, including models of DO. These novel benign urology investigations within the DC- HUB Center will provide fertile ground for future establishment of a George M. O?Brien Urology Research Center Program at UTHSC. The DC-HUB Center will have a major impact on improving healthcare with strong potential to better understand OAB etiology and provide novel therapeutic approaches to help a large population of OAB patients. Given OAB/DO prevalence and the need for new therapies, this research is highly significant. The DC- HUB Center will also establish and maintain an Educational Enrichment Program targeting advanced high school, undergraduate, professional doctor of pharmacy, and medical students, further facilitating outreach to the urology research community.