Ion transport in the distal tubule

Schematic representation of the transport mechanisms in the distal tubule. The Na-K-ATPase pump in the basolateral (peritubular) membrane pumps sodium (Na) out of, and potassium (K) into, the cell. This creates a low intracellular Na concentration, which drives many of the cell's reabsorptive processes. The entry of filtered Na and chloride (Cl) into the cell is mediated by a neutral Na-Cl cotransporter (NCC) in the apical (luminal) membrane. This cotransporter is inhibited by thiazide diuretics. The energy for this process is provided by the favorable inward electrochemical gradient for Na (the intracellular Na concentration is very low and the cell interior is electronegative). The reabsorbed Na that has entered the cell is pumped out by the Na-K-ATPase. The reabsorbed Cl exits via a chloride channel. This is the ClC-Kb channel, which requires interaction with a small protein called barttin to function normally. The late distal tubule and the connecting tubule are also major sites for active calcium (Ca) reabsorption. Ca enters the cell via a calcium channel (TRPV5), owing to the large electrochemical gradient for Ca, and binds inside the cell to calbindinD28K (also called calcium-binding protein [Ca-BP]). After movement across the cell, it then is extruded across the basolateral cell membrane by Ca-ATPase and by 3Na:Ca exchanger (encoded by NCX), which uses the favorable inward electrochemical gradient for Na to drive Ca extrusion.