Up-regulation of acid-gated Na+ channels (ASICs) by cystic fibrosis transmembrane conductance regulator co-expression in Xenopus oocytes

Hong Long Ji, Biljana Jovov, Jian Fu, Latoya R. Bishop, Hannah C. Mebane, Catherine M. Fuller, Bruce A. Stanton, Dale J. Benos

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) functions as both a chloride channel and an epithelial transport regulator, interacting with Na+ (epithelial sodium channel), Cl-, renal outer medullary potassium channel+, and H2O channels and some exchangers (i.e. Na+/H+) and co-transporters (Na+-HCO-3, Na+-K+-2Cl-). Acid-sensitive ion channels (ASICs), members of the epithelial sodium channel/degenerin superfamily, were originally cloned from neuronal tissue, and recently localized in epithelia. Because CFTR has been immunocytochemically and functionally identified in rat, murine, and human brain, the regulation of ASICs by CFTR was tested in oocytes. Our observations show that the proton-gated Na+ current formed by the heteromultimeric ASIC1a/2a channel was up-regulated by wild type but not by ΔF508-CFTR. In contrast, the acid-gated Na+ current associated with either the homomultimeric ASIC1a or ASIC2a channel was not influenced by wild type CFTR. The apparent equilibrium dissociation constant for extracellular Na+ for ASIC1a/2a was increased by CFTR, but CFTR had no effect on the gating behavior or acid sensitivity of ASIC1a/2a. CFTR had no effect on the pH activation of ASIC1a/2a. We conclude that wild type CFTR elevates the acid-gated Na+ current of ASIC1a/2a in part by altering the kinetics of extracellular Na+ interaction.

Original languageEnglish
Pages (from-to)8395-8405
Number of pages11
JournalJournal of Biological Chemistry
Volume277
Issue number10
DOIs
StatePublished - Mar 8 2002

Funding

FundersFunder number
National Institute of Diabetes and Digestive and Kidney DiseasesR01DK056095

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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