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Effect of high-fat diet-induced obesity on the small-conductance Ca2+-activated K+ channel function affecting the contractility of rat detrusor smooth muscle

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Abstract

Purpose

Obesity usually induces overactive bladder (OAB) associated with detrusor overactivity, which is related to increased contractility of the detrusor smooth muscle (DSM). Small-conductance Ca2+-activated K+ (SK) channels play a constitutive role in the regulation of DSM contractility. However, the role of SK channels in the DSM changes in obesity-related OAB is still unknown. Here, we tested the hypothesis that obesity-related OAB is associated with reduced expression and activity of SK channels in DSM and that SK channels activation is a potential treatment for OAB.

Methods

Female Sprague–Dawley rats were fed a normal diet (ND) or a high-fat diet (HFD) and weighed after 12 weeks. Urodynamic studies, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and isometric tension recording were performed.

Results

Increased average body weights and urodynamically demonstrated OAB were observed in HFD rats. qRT-PCR experiments revealed a decrease in the mRNA expression level of SK channel in DSM tissue of the HFD rats. Isometric tension recordings indicated an attenuated relaxation effect of NS309 on the spontaneous phasic and electrical field stimulation-induced contractions that occurred via SK channel activation in HFD DSM strips.

Conclusions

Reduced expression and activity of SK channels in the DSM contribute to obesity-related OAB, indicating that SK channels are a potential therapeutic target for OAB.

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Acknowledgements

Supported by the LNCCC LNCCC-D16-2015 grant to Ning Li; the National Science Foundation of Liaoning Province 2015020493 grant to Ning Li.

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Authors and Affiliations

  1. Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China

    Ning Li, Honglin Ding, Zizheng Li, Yili Liu & Ping Wang

  2. Department of Urology, Affiliated Hospital, Chifeng University, 42 Wangfu Street, Chifeng, Neimeng, China

    Honglin Ding

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  1. Ning Li
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Correspondence to Yili Liu.

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All applicable International, National, and Institutional Guidelines for the care and use of animals were followed.

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Li, N., Ding, H., Li, Z. et al. Effect of high-fat diet-induced obesity on the small-conductance Ca2+-activated K+ channel function affecting the contractility of rat detrusor smooth muscle. Int Urol Nephrol 51, 61–72 (2019). https://doi.org/10.1007/s11255-018-2016-5

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