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.
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Received: 1 October 1997/Revised: 24 December 1997
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Komwatana, P., Dinudom, A., Young, J. et al. Activators of Epithelial Na+ Channels Inhibit Cytosolic Feedback Control. Evidence for the Existence of a G Protein-Coupled Receptor for Cytosolic Na+ . J. Membrane Biol. 162, 225–232 (1998). https://doi.org/10.1007/s002329900360
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DOI: https://doi.org/10.1007/s002329900360