Sodium, bicarbonate, and chloride absorption by the proximal tubule

Abstract

Proximal tubules are lined with epithelial cells that contain Na-K-ATPase in their basolateral cell membrane. The luminal cell membrane contains transport proteins that couple movement of many solutes to the active transport of sodium. The cells are connected by low-resistance junctional complexes that permit passive movement of solutes via a paracellular shunt pathway. Acidification is mediated by a Na/H antiporter localized specifically in the luminal membrane and a chloride-independent, voltage-dependent bicarbonate exit process in the basolateral membrane. The rate of acidification is controlled by the pH of the luminal and peritubular fluids. Reabsorption of NaCl from the high-chloride, low-bicarbonate fluid in the late proximal tubule is approximately 40% passive and 60% active. In proximal straight tubules the active component is entirely by simple rheogenic sodium transport, with chloride absorption driven through the paracellular shunt pathway by the lumen-negative PD. In convoluted tubules the active component is primarily neutral, with both sodium and chloride transported in approximately equivalent amounts through the cell. The mechanisms for neutral NaCl transport across the luminal membrane and for chloride exit across the basolateral membrane are unknown. A reduction in peritubular Starling forces (hydraulic and oncotic pressures) suppresses net proximal reabsorption by two mechanisms: 1) increased paracellular permeability with modest backleak of solutes (bicarbonate, glucose, amino acids) whose luminal concentration falls below their plasma level, and 2) specific inhibition of active neutral transcellular transport of NaCl by reduced peritubular protein concentration by some mechanism other than inhibition of Na-K-ATPase.