ANO1 in urethral SMCs contributes to sex differences in urethral spontaneous tone

Author:

Chen Defang1,Meng Wen2,Shu Ling3,Liu Shuang4,Gu Yongzhong5,Wang Xiaoyan6,Feng Mei47

Affiliation:

1. Department of Outpatient, Central Hospital Affiliated to Shandong First Medical University, Jinan, China

2. Pharmacy Intravenous Admixture Services, Central Hospital Affiliated to Shandong First Medical University, Jinan, China

3. Operating Room, Central Hospital Affiliated to Shandong First Medical University, Jinan, China

4. Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China

5. Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China

6. General Practice Department, College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China

7. Central Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China

Abstract

Stress urinary incontinence (SUI) is more common in women than in men, and sex differences in anatomic structure and physiology have been suggested as causes; however, the underlying cellular and molecular mechanisms remain unclear. The spontaneous tone (STT) of the urethra has been shown to have a fundamental effect on preventing the occurrence of SUI. Here, we investigated whether the urethral STT exhibited sex differences. First, we isolated urethral smooth muscle (USM) and detected STT in female mice and women. No STT was found in male mice or men. Furthermore, caffeine induced increased contractility and intracellular Ca2+ concentration in urethrae from female mice compared with male mice. EACT [an N-aroylaminothiazole, anoctamin-1 (ANO1) activator] elicited increased intracellular Ca2+ concentration and stronger currents in female mice than in male mice. Moreover, ANO1 expression in single USM cells from women and female mice was almost twofold higher than that found in cells from men and male mice. In summary, ANO1 in USM contributes to sex differences in urethral spontaneous tone. This finding may provide new guidance for the treatment of SUI in women and men.

Funder

Natural Scientific Foundation of CHINA

Middle-Aged Scientists of Shandong Province

National Health and Family Planning Commission of the People's Republic of China

Medical and Health Science Technology Development Plan of Shandong Province

Publisher

American Physiological Society

Subject

Physiology

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