The inhibitory effect of Gβγ and Gβ isoform specificity on ENaC activity

Ling Yu, Otor Al-Khalili, Billie Jeanne Duke, James D. Stockand, Douglas C. Eaton, Hui Fang Bao

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Epithelial Na+ channel (ENaC) activity, which determines the rate of renal Na+ reabsorption, can be regulated by G protein-coupled receptors. Regulation of ENaC by Gα-mediated downstream effectors has been studied extensively, but the effect of Gβγ dimers on ENaC is unclear. A6 cells endogenously contain high levels of Gβ1 but low levels of Gβ3, Gβ4, and Gβ5 were detected by Q-PCR. We tested Gγ2 combined individually with Gβ1 through Gβ5 expressed in A6 cells, after which we recorded single-channel ENaC activity. Among the five β and γ2 combinations, β1γ2 strongly inhibits ENaC activity by reducing both ENaC channel number (N) and open probability (Po) compared with control cells. In contrast, the other four β-isoforms combined with γ2 have no significant effect on ENaC activity. By using various inhibitors to probe Gβ1γ2 effects on ENaC regulation, we found that Gβ1γ2-mediated ENaC inhibition involved activation of phospholipase C-β and its enzymatic products that induce protein kinase C and ERK1/2 signaling pathways.

Original languageEnglish (US)
Pages (from-to)F1365-F1373
JournalAmerican Journal of Physiology - Renal Physiology
Volume305
Issue number9
DOIs
StatePublished - Nov 1 2013

Keywords

  • ENaC
  • G protein β γ
  • Phospholipase C
  • Protein kinase C
  • Single channels
  • Subunits

ASJC Scopus subject areas

  • Physiology
  • Urology

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