The Intracellular Region of Fxyd1 is Sufficient to Regulate Cardiac Na/K Atpase.
From: Cardiovascular Division, The Rayne Institute, King’s College London, St. Thomas Hospital, London, SE1 7EH, UK.
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publish Date: May 2007
- ISSN: 1530-6860
- Volume: 21
- Issue: 7
- Pages: 1539-46
- Medium: Internet
- Language: English
- Citation (JAMA): Pavlović Davor, Fuller William, Shattock Michael J, et al. The Intracellular Region of Fxyd1 is Sufficient to Regulate Cardiac Na/K Atpase.. FASEB J. May 2007;21:1539-46
Abstract
FXYD1 is a transmembrane protein predominantly expressed in excitable tissues that associates with and regulates Na/K ATPase. PKA phosphorylates FXYD1 at serine 68 (S68), however, the effects of phosphorylation on Na/K ATPase activity are not fully characterized. The objectives of this study were to characterize Na/K ATPase currents in FXYD1 wild-type (WT) and knockout (KO) adult mouse ventricular myocytes, and investigate the effects of FXYD1 on Na/K ATPase currents using the whole-cell patch-clamp technique. A peptide representing the 19 C-terminal residues of FXYD1 (FXYD1(54-72)) was introduced into the interior of FXYD1 KO and WT myocytes through the patch pipette. K-sensitive Na/K ATPase currents were higher in KO myocytes (2.9+/-0.1 pA/pF; n=4) compared with WT (1.9+/-0.1 pA/pF; n=4). Unphosphorylated FXYD1(54-72), at a concentration of 4 microM, reduced the currents in WT (from 2.1+/-0.1 to 1.3+/-0.1 pA/pF; P<0.05, n=7) and KO (from 2.9+/-0.1 to 1.7+/-0.1 pA/pF; P<0.05, n=5), whereas, 1 microM of FXYD1(54-72) phosphorylated at S68 increased currents in WT (from 1.91+/-0.09 to 3.1+/-0.5 pA/pF; P<0.05, n=6) and KO (from 2.7+/-0.11 to 3.8+/-0.2 pA/pF; P<0.05, n=6) myocytes. Coimmunoprecipitation studies demonstrated that S68 phosphorylated and unphosphorylated FXYD1(54-72) associates with Na/K ATPase alpha1 subunit. We conclude that unphosphorylated FXYD1 inhibits Na/K ATPase, whereas S68 phosphorylated FXYD1 stimulates Na/K ATPase to a level above that seen in the absence of FXYD1.
Mesh Headings (Keywords): Amino Acid Sequence, Animals, Cells, Cultured, Immunoprecipitation, Ion Channel Gating, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Molecular Sequence Data, Myocardium, Phosphoproteins, Phosphorylation, Sodium-Potassium-Exchanging ATPase, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Check for Full Text / PubMed Unique Identifier (PMID): 17283221
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.