Attenuated regulatory function of the small-conductance Ca 2+ -activated K + channel in detrusor smooth muscle cells exc
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UROLOGY - ORIGINAL PAPER
Attenuated regulatory function of the small‑conductance Ca2+‑activated K+ channel in detrusor smooth muscle cells excitability in an obese rat model Jun Hou1 · Ren He2 · Ning Li1 · Yili Liu1 · Ping Wang1 Received: 26 February 2020 / Accepted: 29 April 2020 © Springer Nature B.V. 2020
Abstract Purpose Overactive bladder (OAB) is related to detrusor overactivity (DO), which is caused by the increased detrusor smooth muscle (DSM) cells excitability. Small-conductance C a2+-activated K+ (SK) channels is a fundamental regulator of excitability and contractility in DSM cells. Obesity-related OAB is associated with the decreased expression and regulatory function of SK channels in DSM layer. However, the regulation role of SK channels in obesity-related OAB DSM cell excitability is still unknown. Here, we tested the hypothesis that obesity-related OAB is associated with reduced expression and activity of SK channels in DSM cells. Methods Female Sprague–Dawley rats were fed a normal diet (ND) or a high-fat diet (HFD) and weighed after 12 weeks. We performed urodynamic study, single-cell quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and patch-clamp electrophysiology. Results Increased average body weights and urodynamically demonstrated OAB were observed in HFD rats. Single-cell qRT-PCR experiments discovered the decreased mRNA expression level of SK channel in DSM cell from HFD rats. Patchclamp studies revealed that NS309, a SK channel activator, had an attenuated effect on membrane potential hyperpolarization in HFD DSM cells. In addition, the reduced whole cell SK channel currents were recorded in HFD DSM cells. Conclusions Attenuated SK channels expression and function, which results in the increased DSM cells excitability and contributes to DO, is discovered in obesity-related OAB DSM cells, suggesting that SK channels might be potential therapeutic targets to control OAB. Keywords SK channel · Overactive bladder · Detrusor smooth muscle · High-fat diet · Obesity
Introduction Obesity has become a major global health challenge and the worldwide prevalence of obesity has nearly tripled between 1975 and 2016 [1]. Obesity is directly associated with medical co-morbidities such as cardiovascular disease, diabetes, cancer and depression, and adversely affects the quality of life [2, 3]. Epidemiological studies document obesity as a * Ning Li air‑[email protected] 1
Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China
Department of Urology, The 79th Army Hospital, 148 Weiguo Road, Baita District, Liaoyang, Liaoning, China
2
strong independent risk factor for overactive bladder (OAB) [4–6]. OAB is characterized by urgency, with or without urgency urinary incontinence and is usually associated with urodynamically demonstrable detrusor overactivity (DO) [7, 8]. OAB has a negative effect on the quality of life of patients with an increased incidence. The potential etiology and contribut
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