Mechanism underlying flow stimulation of sodium absorption in the mammalian collecting duct.

American Journal of Physiology. Renal Physiology
Tetsuji MorimotoThomas R Kleyman

Abstract

Vectorial Na(+) absorption across the aldosterone-sensitive distal nephron plays a key role in the regulation of extracellular fluid volume and blood pressure. Within this nephron segment, Na(+) diffuses from the urinary fluid into principal cells through an apical, amiloride-sensitive, epithelial Na(+) channel (ENaC), which is considered to be the rate-limiting step for Na(+) absorption. We have reported that increases in tubular flow rate in microperfused rabbit cortical collecting ducts (CCDs) lead to increases in net Na(+) absorption and that increases in laminar shear stress activate ENaC expressed in oocytes by increasing channel open probability. We therefore examined whether flow stimulates net Na(+) absorption (J(Na)) in CCDs by increasing channel open probability or by increasing the number of channels at the apical membrane. Both baseline and flow-stimulated J(Na) in CCDs were mediated by ENaC, as J(Na) was inhibited by benzamil. Flow-dependent increases in J(Na) were observed following treatment of tubules with reagents that altered membrane trafficking by disrupting microtubules (colchicine) or Golgi (brefeldin A). Furthermore, reducing luminal Ca(2+) concentration ([Ca(2+)]) or chelating intracellular [Ca(2+)] wit...Continue Reading

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