Feedback inhibition of epithelial Na + channels in Xenopus oocytes does not require G 0 or G i2 proteins

Abstract

Regulation of amiloride-sensitive epithelial Na + channels (ENaC) is a prerequisite for coordination of electrolyte transport in epithelia. Downregulation of Na + conductance occurs when the intracellular Na + concentration is increased during reabsorption of electrolytes, known as feedback inhibition. Recent studies have demonstrated the involvement of αG 0 and αG i2 proteins in the feedback control of ENaC in mouse salivary duct cells. In this report, we demonstrate that Na + feedback inhibition is also present in Xenopus oocytes after expression of rat α,β,γ-ENaC. Interfering with intracellular αG 0 or αG i2 signaling by coexpression of either constitutively active αG 0/αG i2 or dominant negative αG 0/αG i2 and by coinjecting sense or antisense oligonucleotides for αG 0 had no impact on Na + feedback. Moreover, no evidence for involvement of the intracellular G protein cascade was found in experiments in which a regulator of G protein signaling (RGS3) or β-adrenergic receptor kinase (βARK) was coexpressed together with α,β,γ-ENaC. Although some experiments suggest the presence of an intracellular Na + receptor, we may conclude that Na + feedback in Xenopus oocytes is different from that described for salivary duct cells in that it does not require G protein signaling.