Analysis of Aprotinin, a Protease Inhibitor, Action on the Trafficking of Epithelial Na+ Channels (ENaC) in Renal Epithelial Cells Using a Mathematical Model

作者：Sasamoto Kouhei; Marunaka Rie; Niisato Naomi; Sun Hongxin; Taruno Akiyuki; Pezzotti Giuseppe; Yamamoto Toshiro; Kanamura Narisato; Zhu Wenliang; Nishio Kyosuke; Inui Toshio; Eaton Douglas C; Marunaka Yoshinori^*

来源：Cellular Physiology and Biochemistry, 2017, 41(5): 1865-1880.

DOI：10.1159/000471934

• ENaC
• Transcellular Na+ reabsorption
• Mathematical model
• Simulation
• Epithelium

Background/Aim: Epithelial Na+ channels (ENaC) play a crucial role in control of blood pressure by regulating renal Na+ reabsorption. Intracellular trafficking of ENaC is one of the key regulators of ENaC function, but a quantitative description of intracellular recycling of endogenously expressed ENaC is unavailable. We attempt here to provide a model for intracellular recycling after applying a protease inhibitor under hypotonic conditions. Methods: We simulated the ENaC-mediated Na+ transport in renal epithelial A6 cells measured as short-circuit currents using a four-state mathematical ENaC trafficking model. Results: We developed a four-state mathematical model of ENaC trafficking in the cytosol of renal epithelial cells that consists of: an insertion state of ENaC that can be trafficked to the apical membrane state (insertion rate); an apical membrane state of ENaC conducting Na+ across the apical membrane; a recycling state containing ENaC that are retrieved from the apical membrane state (endocytotic rate) and then to the insertion state (recycling rate) communicating with the apical membrane state or to a degradation state (degradation rate). We studied the effect of aprotinin (a protease inhibitor) blocking protease-induced cleavage of the extracellular loop of.

• 出版日期2017