Cellular Mechanism Underlying Hydrogen Sulfide Mediated Epithelial K+ Secretion in Rat Epididymis
Cellular Mechanism Underlying Hydrogen Sulfide Mediated Epithelial K+ Secretion in Rat Epididymis
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硫化氢介导大鼠附睾上皮钾分泌的细胞机制
DOI：
10.3389/fphys.2018.01886
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发表时间：
2019-01-07
影响因子：
4
通讯作者：
Zhou, Wen-Liang
中科院分区：
文献类型：
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作者：
Gao, Dong-Dong;Xu, Jia-Wen;Zhou, Wen-Liang
作为一种新型的气体递质，硫化氢(H_2S)具有多种生理作用，包括松弛血管和促进跨上皮细胞离子转运。然而，硫化氢在男性生殖系统中的促分泌功能在很大程度上仍不清楚。本研究的目的是阐明硫化氢在调节大鼠附睾腔内离子微环境中的可能作用，这是精子储存所必需的。结果表明，内源性硫化氢产生酶胱硫醚β-合成酶(CBS)和胱硫醚γ-裂解酶(CSE)均在大鼠附精中表达。CBS主要表达于上皮细胞，而CSE主要表达于平滑肌细胞。CBS和CSE的相对表达水平从附睾头到附睾尾逐渐升高，与内源性H_2S的产生逐渐增加相平行。采用短路电流(I-SC)、细胞内离子浓度测定和在体大鼠附睾微灌流等方法，研究了硫化氢对附睾上皮细胞离子转运的影响。我们的实验结果表明，H_2S通过三磷酸腺苷敏感性钾通道(K-ATP)和大电导钙激活钾通道(BKCa)诱导跨上皮钾分泌。瞬时受体电位香草素4(TRPV4)通道介导的钙内流参与了BKCa通道的激活。体内实验进一步证明，H_2S可促进大鼠附睾上皮细胞K+分泌。抑制内源性H_2S合成可使尾部附睾腔内液K~+浓度显著降低。此外，我们的数据还表明，细胞外高K+浓度以非pH依赖的方式主动抑制附睾尾部精子的活力。综上所述，本研究表明，H_2S通过促进跨上皮K~+的分泌，在附睾腔内液中形成高K~+浓度，这可能有助于维持附睾尾精子在射精前处于静止休眠状态。
As a novel gasotransmitter, hydrogen sulfide (H2S) elicits various physiological actions including smooth muscle relaxation and promotion of transepithelial ion transport. However, the pro-secretory function of H2S in the male reproductive system remains largely unclear. The aim of this study is to elucidate the possible roles of H2S in modulating rat epididymal intraluminal ionic microenvironment essential for sperm storage. The results revealed that endogenous H2S-generating enzymes cystathionine beta-synthetase (CBS) and cystathionine gamma-lyase (CSE) were both expressed in rat epididymis. CBS located predominantly in epithelial cells whilst CSE expressed primarily in smooth muscle cells. The relative expression level of CBS and CSE escalated from caput to cauda regions of epididymis, which was paralleled to the progressively increasing production of endogenous H2S. The effect of H2S on epididymal epithelial ion transportation was investigated using short-circuit current (I-SC), measurement of intracellular ion concentration and in vivo rat epididymal microperfusion. Our data showed that H2S induced transepithelial K+ secretion via adenosine triphosphatesensitive K+ (K-ATP) channel and large conductance Ca2+ -activated K+ (BKCa) channel. Transient receptor potential vanilloid 4 (TRPV4) channel-mediated Ca2+ influx was implicated in the activation of BKCa channel. in vivo studies further demonstrated that H2S promoted K+ secretion in rat epididymal epithelium. Inhibition of endogenous H2S synthesis caused a significant decrease in K+ concentration of cauda epididymal intraluminal fluid. Moreover, our data demonstrated that high extracellular K+ concentration actively depressed the motility of cauda epididymal sperm in a pH-independent manner. Collectively, the present study demonstrated that H2S was vital to the formation of high K+ concentration in epididymal intraluminal fluid by promoting the transepithelial K+ secretion, which might contribute to the maintenance of the cauda epididymal sperm in quiescent dormant state before ejaculation.