{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T10:43:48Z","timestamp":1793357028116,"version":"4.5.0"},"reference-count":45,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:p>Vectorial Na<jats:sup>+<\/jats:sup>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<jats:sup>+<\/jats:sup>diffuses from the urinary fluid into principal cells through an apical, amiloride-sensitive, epithelial Na<jats:sup>+<\/jats:sup>channel (ENaC), which is considered to be the rate-limiting step for Na<jats:sup>+<\/jats:sup>absorption. We have reported that increases in tubular flow rate in microperfused rabbit cortical collecting ducts (CCDs) lead to increases in net Na<jats:sup>+<\/jats:sup>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<jats:sup>+<\/jats:sup>absorption ( J<jats:sub>Na<\/jats:sub>) in CCDs by increasing channel open probability or by increasing the number of channels at the apical membrane. Both baseline and flow-stimulated J<jats:sub>Na<\/jats:sub>in CCDs were mediated by ENaC, as J<jats:sub>Na<\/jats:sub>was inhibited by benzamil. Flow-dependent increases in J<jats:sub>Na<\/jats:sub>were observed following treatment of tubules with reagents that altered membrane trafficking by disrupting microtubules (colchicine) or Golgi (brefeldin A). Furthermore, reducing luminal Ca<jats:sup>2+<\/jats:sup>concentration ([Ca<jats:sup>2+<\/jats:sup>]) or chelating intracellular [Ca<jats:sup>2+<\/jats:sup>] with BAPTA did not prevent the flow-dependent increase in J<jats:sub>Na<\/jats:sub>. Extracellular trypsin has been shown to activate ENaC by increasing channel open probability, and we observed that trypsin significantly enhanced J<jats:sub>Na<\/jats:sub>when tubules were perfused at a slow flow rate. However, trypsin did not further enhance J<jats:sub>Na<\/jats:sub>in CCDs perfused at fast flow rates. Similarly, the shear-induced increase in benzamil-sensitive J<jats:sub>Na<\/jats:sub>in oocytes expressing protease resistance ENaC mutants was similar to that of controls. Our results suggest the rise in J<jats:sub>Na<\/jats:sub>accompanying increases in luminal flow rates reflects an increase in channel open probability.<\/jats:p>","DOI":"10.1152\/ajprenal.00514.2005","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T04:06:31Z","timestamp":1146024391000},"page":"F663-F669","source":"Crossref","is-referenced-by-count":109,"title":["Mechanism underlying flow stimulation of sodium absorption in the mammalian collecting duct"],"prefix":"10.1152","volume":"291","author":[{"given":"Tetsuji","family":"Morimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Woda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo 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