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The Journal of Membrane Biology

, Volume 162, Issue 3, pp 225–232 | Cite as

Activators of Epithelial Na+ Channels Inhibit Cytosolic Feedback Control. Evidence for the Existence of a G Protein-Coupled Receptor for Cytosolic Na+

  • P.  Komwatana
  • A.  Dinudom
  • J.A.  Young
  • D.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 G o and G i 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 α-subunit of G o in the pipette solution, we conclude that these agents act by blocking a previously unrecognized intracellular Na+ receptor.

Keywords: Amiloride — Salivary gland — Na+ current — Para-chloromercuriphenylsulfonate — Benzimidazolylguanidinium 

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Copyright information

© Springer-Verlag New York Inc. 1998

Authors and Affiliations

  • P.  Komwatana
    • 1
  • A.  Dinudom
    • 1
  • J.A.  Young
    • 1
  • D.I.  Cook
    • 1
  1. 1.Department of Physiology, University of Sydney, NSW 2006, AustraliaAU

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