Regulation of epithelial sodium channels by short actin filaments

Bakhram K. Berdiev, Adriana G. Prat, Horacio F. Cantiello, Dennis A. Ausiello, Catherine M. Fuller, Biljana Jovov, Dale J. Benos, Iskander I. Ismailov

Research output: Contribution to journalArticlepeer-review

155 Citations (Scopus)


Cytoskeletal elements play an important role in the regulation of ion transport in epithelia. We have studied the effects of actin filaments of different length on the α, β, γ-rENaC (rat epithelial Na+ channel) in planar lipid bilayers. We found the following. 1) Short actin filaments caused a 2-fold decrease in unitary conductance and a 2-fold increase in open probability (P(o)) of α,β,γ-rENaC. 2) α,β,γ-rENaC could be transiently activated by protein kinase A (PKA) plus ATP in the presence, but not in the absence, of actin. 3) ATP in the presence of actin was also able to induce a transitory activation of α,β,γ,-rENaC, although with a shortened time course and with a lower magnitude of change in P(o). 4) DNase I, an agent known to prohibit elongation of actin filaments, prevented activation of α,β,γ-rENaC by ATP or PKA plus ATP. 5) Cytochalasin D, added after rundown of α,β,γ-rENaC activity following ATP or PKA plus ATP treatment, produced a second transient activation of α,β,γ-rENaC. 6) Gelsolin, a protein that stabilizes polymerization of actin filaments at certain lengths, evoked a sustained activation of α,β,γ-rENaC at actin/gelsolin ratios of <32:1, with a maximal effect at an actin/gelsolin ratio of 2:1. These results suggest that short actin filaments activate α,β,γ-rENaC. PKA-mediated phosphorylation augments activation of this channel by decreasing the rate of elongation of actin filaments. These results are consistent with the hypothesis that cloned α,β,γ-rENaCs form a core conduction unit of epithelial Na+ channels and that interaction of these channels with other associated proteins, such as short actin filaments, confers regulation to channel activity.

Original languageEnglish
Pages (from-to)17704-17710
Number of pages7
JournalJournal of Biological Chemistry
Issue number30
Publication statusPublished - 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Regulation of epithelial sodium channels by short actin filaments'. Together they form a unique fingerprint.

Cite this