In:
American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 303, No. 1 ( 2012-07-01), p. F45-F55
Abstract:
In cortical collecting ducts (CCDs) perfused in vitro, inhibiting the epithelial Na + channel (ENaC) reduces Cl − absorption. Since ENaC does not transport Cl − , the purpose of this study was to determine how ENaC modulates Cl − absorption. Thus, Cl − absorption was measured in CCDs perfused in vitro that were taken from mice given aldosterone for 7 days. In wild-type mice, we observed no effect of luminal hydrochlorothiazide on either Cl − absorption or transepithelial voltage ( V T ). However, application of an ENaC inhibitor [benzamil (3 μM)] to the luminal fluid or application of a Na + -K + -ATPase inhibitor to the bath reduced Cl − absorption by ∼66–75% and nearly obliterated lumen-negative V T . In contrast, ENaC inhibition had no effect in CCDs from collecting duct-specific ENaC-null mice (Hoxb7:CRE, Scnn1a loxlox ). Whereas benzamil-sensitive Cl − absorption did not depend on CFTR, application of a Na + -K + -2Cl − cotransport inhibitor (bumetanide) to the bath or ablation of the gene encoding Na + -K + -2Cl − cotransporter 1 (NKCC1) blunted benzamil-sensitive Cl − absorption, although the benzamil-sensitive component of V T was unaffected. In conclusion, first, in CCDs from aldosterone-treated mice, most Cl − absorption is benzamil sensitive, whereas thiazide-sensitive Cl − absorption is undetectable. Second, benzamil-sensitive Cl − absorption occurs by inhibition of ENaC, possibly due to elimination of lumen-negative V T . Finally, benzamil-sensitive Cl − flux occurs, at least in part, through transcellular transport through a pathway that depends on NKCC1.
Type of Medium:
Online Resource
ISSN:
1931-857X
,
1522-1466
DOI:
10.1152/ajprenal.00030.2012
Language:
English
Publisher:
American Physiological Society
Publication Date:
2012
detail.hit.zdb_id:
1477287-5
