A mathematical model of rat ascending Henle limb. III. Tubular function

作者：Weinstein Alan M^*

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2010, 298(3): F543-F556.

DOI：10.1152/ajprenal.00232.2009

• NKCC
• KCC
• NHE3
• sodium transport
• potassium transport
• ammonia
• Bartter's syndrome
• loop diuretic

Weinstein AM. A mathematical model of rat ascending Henle limb. III. Tubular function. Am J Physiol Renal Physiol 298: F543-F556, 2010. First published November 18, 2009; doi:10.1152/ajprenal.00232.2009.-K(+) plays a catalytic role in AHL Na(+) reabsorption via Na(+)-K(+)-2Cl(-) cotransporter (NKCC2), recycling across luminal K(+) channels, so that luminal K(+) is not depleted. Based on models of the ascending Henle limb (AHL) epithelium, it has been hypothesized that NH(4)(+) may also catalyze luminal Na(+) uptake. This hypothesis requires that luminal NH(4)(+) not be depleted, implying replenishment via either direct secretion of NH(4)(+), or NH(3) in parallel with a proton. In the present work, epithelial models of rat medullary and cortical AHL (Weinstein AM, Krahn TA. Am J Physiol Renal Physiol 298: F000-F000, 2009) are configured as tubules and examined in simulations of function in vitro and in vivo to assess the feasibility of a catalytic role for NH(4)(+) in Na(+) reabsorption. Modulation of Na(+) transport is also examined by peritubular K(+) concentration and by Bartter-type transport defects in NKCC2 (type 1), in luminal membrane K(+) channels (type 2), and in peritubular Cl(-) channels (type 3). It is found that a catalytic role for NH(4)(+), which is significant in magnitude (relative to K(+)), is quantitatively realistic, in terms of uptake via NKCC2, and in terms of luminal membrane ammonia backflux. Simulation of a 90% NKCC2 defect is predicted to double distal Na(+) delivery; it is also predicted to increase distal acid delivery (principally as NH(4)(+)). With doubling of medullary K(+), the model predicts a 30% increase in distal Na(+) delivery, but in this case there is a decrease in AHL acidification. This effect of peritubular K(+) on proton secretion appears to be akin to type 3 Bartter's pathophysiology, in which there is decreased peritubular HCO(3)(-) exit, cytosolic alkalinization, and a consequent decrease in luminal proton secretion by NHE3. One consequence of overlapping and redundant roles for K(+) and NH(4)(+), is a blunted impact of luminal membrane K(+) permeability on overall Na(+) reabsorption, so that type 2 Bartter pathophysiology is not well captured by the model.

• 出版日期2010-3