Attenuated BK channel function promotes overactive bladder in a rat model of obesity

Abstract

Overactive bladder (OAB) is mostly observed in obese individuals, and is associated with enhanced excitability and contractility of the detrusor smooth muscle (DSM). Large-conductance voltage- and Ca²⁺-activated K⁺ (BK) channels reduce the excitability and contractility of the DSM. We tested whether obesity-induced OAB is associated with altered BK channel expression and activity in the DSM. Seven-week-old female Sprague-Dawley rats (N=80) were fed a normal or high-fat diet (HFD) for 12 weeks. HFD-fed rats exhibited a higher average bodyweight and urodynamically established detrusor overactivity. mRNA levels of the Kcnma1 (BKα subunit) and Kcnmb1 (BKβ1 subunit) in whole tissues and cells from the DSM were reduced in HFD-fed rats. A selective BK channel opener, NS1619, was then applied to DSM cells from the two groups of rats. Patch-clamp techniques revealed that spontaneous transient outward currents, NS1619-induced activation of spontaneous transient outward currents, and whole-cell BK currents, as well as NS1619-induced membrane hyperpolarization, were attenuated in DSM cells from HFD-fed rats. The relaxation effect of NS1619 on contractility was reduced in DSM strips from HFD-fed rats. Thus, impaired expression of Kcnma1 and Kcnmb1 in the DSM contributes to obesity-induced OAB, suggesting that BK channels could be a useful treatment targets in OAB.