Cellular mechanisms underlying carbon monoxide stimulated anion secretion in rat epididymal epithelium

• Published in: Nitric oxide 2020-08, Vol.100-101, p.30-37
• Main Authors: Peng, Lei, Gao, Dong-Dong, Xu, Jia-Wen, Xu, Jian-Bang, Ke, Li-Jiao, Qiu, Zhuo-Er, Zhu, Yun-Xin, Zhang, Yi-Lin, Zhou, Wen-Liang
• Format: Article
• Language: English
• Subjects: Animals; Anion secretion; CaCC; Carbon Monoxide - metabolism; CFTR; Chloride Channels - metabolism; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Epididymal epithelium; Epididymis - drug effects; Epididymis - physiology; Epithelium - drug effects; Epithelium - physiology; Heme Oxygenase (Decyclizing) - metabolism; Ion Transport - drug effects; Ion Transport - physiology; Male; Organometallic Compounds - pharmacology; Rats, Sprague-Dawley
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2020.04.004

Epididymal epithelium possesses active ion transport properties conducive to the maintenance of appropriate epididymal intraluminal microenvironment. The endogenous gasotransmitter carbon monoxide (CO) regulates numerous cellular processes including water and electrolyte transport in various epithelia. However, the functional role of CO in epididymal epithelium is still elusive. This study aims to explore the potential regulatory effect of CO on transepithelial ion transport in rat epididymis. Using qPCR technique, we verified that endogenous CO synthase heme oxygenase 1 was expressed in rat caput, corpus, and cauda epididymis. In addition, endogenous CO was detected in rat cauda epididymis. Ussing chamber experiments showed that CORM-2, a CO donor, induced an increase of the short-circuit current (ISC) in a concentration-dependent manner in rat cauda epididymal epithelium. The ISC response could be abrogated by removing the ambient Cl− or HCO3−. Interfering with the cAMP signaling pathway or blocking cystic fibrosis transmembrane regulator (CFTR) partially suppressed the CO-stimulated ISC response. Moreover, the CO-evoked ISC response was significantly attenuated by blocking Ca2+-activated Cl− channel (CaCC) or chelating intracellular Ca2+. Elevation of intracellular Ca2+ level was also observed after CO stimulation in rat cauda epididymal epithelial cells. Collectively, this study demonstrated that CO stimulated anion secretion via activation of CFTR and CaCC in rat cauda epididymal epithelium, which might contribute to the formation of the appropriate microenvironment essential for sperm storage. •The endogenous CO synthase heme oxygenase 1 was expressed in rat epididymis.•The endogenous CO was produced in rat cauda epididymis.•CO facilitated transepithelial anion secretion in rat cauda epididymal epithelium via activation of CFTR and CaCC.•CO increased [Ca2+]i of rat cauda epididymal epithelial cells via PLC/IP3 pathways.