PMID: 9543495May 16, 1998Paper

Activators of epithelial Na+ channels inhibit cytosolic feedback control. Evidence for the existence of a G protein-coupled receptor for cytosolic Na+

The Journal of Membrane Biology
P KomwatanaD I Cook

Abstract

We have previously shown that epithelial Na+ channels in mouse mandibular gland duct cells are controlled by cytosolic Na+ and Cl-, acting, respectively, via Go and Gi proteins. Since we found no evidence for control of epithelial Na+ channels by extracellular Na+ ([Na+]o), our findings conflicted with the long-held belief that Na+ channel activators, such as sulfhydryl reagents, like para-chloromercuriphenylsulfonate (PCMPS), and amiloride analogues, like benzimidazolylguanidinium (BIG) and 5-N-dimethylamiloride (DMA), induce their effects by blocking an extracellular channel site which otherwise inhibits channel activity in response to increasing [Na+]o. Instead, we now show that PCMPS acts by rendering epithelial Na+ channels refractory to inhibition by activated G proteins, thereby eliminating the inhibitory effects of cytosolic Na+ and Cl- on Na+ channel activity. We also show that BIG, DMA, and amiloride itself, when applied from the cytosolic side of the plasma membrane, block feedback inhibition of Na+ channels by cytosolic Na+, while leaving inhibition by cytosolic Cl- unaffected. Since the inhibitory effects of BIG and amiloride are overcome by the inclusion of the activated alpha-subunit of Go in the pipette solution...Continue Reading

Citations

Sep 7, 2007·Pflügers Archiv : European journal of physiology·Anil Mehta
Jul 30, 2002·European Journal of Pharmacology·Timothy J BurtonDouglas R Ferguson
Jan 17, 2008·Clinical and Experimental Pharmacology & Physiology·Il-Ha LeeAnuwat Dinudom
Feb 13, 2009·Neuro-Signals·Meisheng Jiang, Neil S Bajpayee
Feb 1, 2008·Journal of the American Society of Nephrology : JASN·Scott S P WildmanRobert J Unwin
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·H IshibashiD I Cook
Jun 17, 1998·Proceedings of the National Academy of Sciences of the United States of America·A DinudomD I Cook
Apr 15, 2000·The Journal of Physiology·S J RammingerS M Wilson
Jan 1, 2004·The Journal of Biological Chemistry·Shaohu ShengThomas R Kleyman
Jul 20, 2005·The Journal of Biological Chemistry·Tanja BachhuberKarl Kunzelmann
Jul 8, 2005·Journal of the American Society of Nephrology : JASN·Scott S WildmanRobert J Unwin
Apr 27, 2002·The Journal of Biological Chemistry·Keith NehrkeJames E Melvin
Sep 13, 2001·American Journal of Physiology. Renal Physiology·L DijkinkR J Bindels
Nov 10, 2017·Annual Review of Physiology·Thomas R KleymanRebecca P Hughey
Nov 8, 2002·Biochimica Et Biophysica Acta·Mikael SchnizlerWolfgang Clauss
Jan 25, 2003·Biochimica Et Biophysica Acta·Mikael SchnizlerWolfgang Clauss

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