Research Paper Volume 11, Issue 16 pp 6199—6216

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

Ning Li 1, , Honglin Ding 1, 2, , Peng Zhang 3, , Zizheng Li 1, , Yili Liu 1, , Ping Wang 1, ,

  • 1 Department of Urology, Fourth Affiliated Hospital, China Medical University, Shenyang, Liaoning, China
  • 2 Department of Urology, Affiliated Hospital, Chifeng University, Chifeng, Neimeng, China
  • 3 Department of General Surgery, Shenyang 242 Hospital, Shenyang, Liaoning, China

received: March 18, 2019 ; accepted: August 10, 2019 ; published: August 21, 2019 ;

https://doi.org/10.18632/aging.102182
How to Cite

Copyright © 2019 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

BK: large-conductance voltage- and Ca2+-activated K+; BKα: BK channel α-subunit; BKβ1: BK channel β1-subunit; BKβ2: BK channel β2-subunit; BKβ3: BK channel β3-subunit; BKβ4: BK channel β4-subunit; DMSO: dimethyl sulfoxide; DSM: detrusor smooth muscle; EFS: electrical field stimulation; HFD: high-fat diet; ND: normal diet; NVCs: non-voiding contractions; OAB: overactive bladder; PBOO: partial bladder outlet obstruction; qRT-PCR: quantitative real-time polymerase chain reaction; SEM: standard error of the mean; STOCs: spontaneous transient outward currents.