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NS11021, a BK Channel Opener, Effects Significant Changes on Mouse Urinary Bladder Function During Urodynamics
Hagop Sarkissian, Tom Heppner, Peter Zvara, Mark Plante, Mark Nelson
University of Vermont, Burlington, VT

Large conductance Ca2+ activated potassium (BK) channels are ubiquitous throughout excitable and non-excitable tissues. BK knockout mice exhibit urinary frequency and urinary leakage. Their bladders show increased intravesicular pressures, increased excitability and spontaneous contractions. Therefore, the current project sought to investigate a novel BK channel opener, NS11021, and examine its effect on bladder function in partially obstructed (pBOO), overactive and normal controls.
Materials & Methods:
Bladder domes of pBOO and normal, C57BL/6 mice, were implanted with polyethylene tubing. Subsequently, conscious, continuous cystometrography was performed. CMG had three separate phases: control/saline infusion (0.75mL/hr), an established rest period, then, continuous intravesicular infusion phase of 30microM of NS11021 solution.
In mice with pBOO or with overactivity on CMG (n=5), NS11021 infusion improved CMG parameters significantly. Quantitatively, a 43% increase in threshold pressure (p<0.001), an 82% increase in intermicturition interval (p<0.001), a 32% decrease in filling pressure (p<0.001) and a 9% decrease in peak pressure. In normal mice, i.e. those without overactivity, NS11021 had no effect.

In mice with pBOO and overactivity, intravesicle infusion of NS11021, seemed to effect significant functional changes in bladder characteristics on CMG, including marked decreases of phasic, non-voiding contractions. These Results may have translational implications in the future for the treatment of bladder overactivity in certain patient populations.

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