1. Collecting duct-specific endothelin B receptor knockout increases ENaC activity
- Author
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James D. Stockand, Donald E. Kohan, Elena Mironova, and Vladislav Bugaj
- Subjects
Male ,Epithelial sodium channel ,medicine.medical_specialty ,Physiology ,Natriuresis ,Amiloride ,Excretion ,Mice ,Internal medicine ,Epithelial Sodium Channel Blockers ,medicine ,Animals ,Kidney Tubules, Collecting ,Epithelial Sodium Channels ,Receptor ,Endothelin B receptor ,Mice, Knockout ,Membrane Transporters, Ion Channels and Pumps ,Endothelin-1 ,Chemistry ,Sodium ,Cell Biology ,respiratory system ,Receptor, Endothelin B ,Endothelin 1 ,Up-Regulation ,medicine.anatomical_structure ,Endocrinology ,Hypertension ,cardiovascular system ,Female ,Endothelin receptor ,Duct (anatomy) ,Sodium retention ,circulatory and respiratory physiology - Abstract
Collecting duct (CD)-derived endothelin-1 (ET-1) acting via endothelin B (ETB) receptors promotes Na+ excretion. Compromise of ET-1 signaling or ETB receptors in the CD cause sodium retention and increase blood pressure. Activity of the epithelial Na+ channel (ENaC) is limiting for Na+ reabsorption in the CD. To test for ETB receptor regulation of ENaC, we combined patch-clamp electrophysiology with CD-specific knockout (KO) of endothelin receptors. We also tested how ET-1 signaling via specific endothelin receptors influences ENaC activity under differing dietary Na+ regimens. ET-1 significantly decreased ENaC open probability in CD isolated from wild-type (WT) and CD ETA KO mice but not CD ETB KO and CD ETA/B KO mice. ENaC activity in WT and CD ETA but not CD ETB and CD ETA/B KO mice was inversely related to dietary Na+ intake. ENaC activity in CD ETB and CD ETA/B KO mice tended to be elevated under all dietary Na+ regimens compared with WT and CD ETA KO mice, reaching significance with high (2%) Na+ feeding. These results show that the bulk of ET-1 inhibition of ENaC activity is mediated by the ETB receptor. In addition, they could explain the Na+ retention and elevated blood pressure observed in CD ET-1 KO, CD ETB KO, and CD ETA/B KO mice consistent with ENaC regulation by ET-1 via ETB receptors contributing to the antihypertensive and natriuretic effects of the local endothelin system in the mammalian CD.
- Published
- 2012