Mathematical model of epithelial Cl ‐ secretion determining activity of electro‐neutral ion transporter (892.11)

Epithelial Cl‐ secretion plays key roles in prevention of our body from environmental changes by generating driving forces for transepithelial transport of ions and water; for instance, the Cl‐‐secretion‐driven water movement plays an essential role in protection of our body from bacterial and viral infection by producing the liquid covering epithelial apical membrane surface. Transcellular Cl‐ secretion across the epithelium is composed of two steps; 1) the Cl‐ entry step across the basolateral membrane and 2) the Cl‐ releasing step across the apical membrane. The purpose of the present study was to establish a mathematical model expressing characteristics of transcellular Cl‐ secretion via the following three pathways: 1) the Cl‐ entry step across the basolateral membrane into the intracellular space via an electro‐neutral ion transporter, Na+/K+/2Cl‐ cotransporter (NKCC); 2) the Cl‐ secretion step across the apical membrane from the intracellular space via Cl‐ channels; 3) the Cl‐ recycling step across the basolateral membrane via Cl‐ channels. We measured the transcellular Cl‐ secretion by an electrophysiological technique (short‐circuit current) and the apical/basolateral Cl‐ conductance in Ussing chamber by detecting them as NPPB (Cl‐ channel blocker)‐sensitive short‐circuit current and conductance. The mathematical model established in the present study is useful to determine the activity of electro‐neutral ion transporter, NKCC, by combing electrophysiological techniques, providing deep understandings in the research field of epithelial ion transport. Supported by JSPS.