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Am J Physiol Renal Physiol 280: F1010-F1018, 2001;
0363-6127/01 $5.00
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Vol. 280, Issue 6, F1010-F1018, June 2001

Epithelial Na+ channels are regulated by flow

Lisa M. Satlin1,*, Shaohu Sheng2,*, Craig B. Woda1, and Thomas R. Kleyman2

1 Department of Pediatrics, Mount Sinai School of Medicine, New York, New York 10029-6574; and 2 Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261

Na+ absorption in the renal cortical collecting duct (CCD) is mediated by apical epithelial Na+ channels (ENaCs). The CCD is subject to continuous variations in intraluminal flow rate that we speculate alters hydrostatic pressure, membrane stretch, and shear stress. Although ENaCs share limited sequence homology with putative mechanosensitive ion channels in Caenorhabditis elegans, controversy exists as to whether ENaCs are regulated by biomechanical forces. We examined the effect of varying the rate of fluid flow on whole cell Na+ currents (INa) in oocytes expressing mouse alpha ,beta ,gamma -ENaC (mENaC) and on net Na+ absorption in microperfused rabbit CCDs. Oocytes injected with mENaC but not water responded to the initiation of superfusate flow (to 4-6 ml/min) with a reversible threefold stimulation of INa without a change in reversal potential. The increase in INa was variable among oocytes. CCDs responded to a threefold increase in rate of luminal flow with a twofold increase in the rate of net Na+ absorption. An increase in luminal viscosity achieved by addition of 5% dextran to the luminal perfusate did not alter the rate of net Na+ absorption, suggesting that shear stress does not influence Na+ transport in the CCD. In sum, our data suggest that flow stimulation of ENaC activity and Na+ absorption is mediated by an increase in hydrostatic pressure and/or membrane stretch. We propose that intraluminal flow rate may be an important regulator of channel activity in the CCD.

epithelial sodium channel; ROMK; collecting duct; transepithelial transport; oocyte

* L. M. Satlin and S. Sheng contributed equally to this study.




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