The intracellular region of FXYD1 is sufficient to regulate cardiac Na/K ATPase

Pavlović, D., Fuller, W. and Shattock, M. J. (2008) The intracellular region of FXYD1 is sufficient to regulate cardiac Na/K ATPase. FASEB Journal, 21(7), pp. 1539-1546. (doi: 10.1096/fj.06-7269com) (PMID:17283221)

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 (FXYD154–72) 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 FXYD154–72, at a concentration of 4 μM, 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 μM of FXYD154–72 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 FXYD154–72 associates with Na/K ATPase α1 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.—Pavlović, D., Fuller, W., and Shattock, M. J. The intracellular region of FXYD1 is sufficient to regulate cardiac Na/K ATPase.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Fuller, Professor Will
• Authors: Pavlović, D., Fuller, W., and Shattock, M. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: FASEB Journal
• Publisher: Federation of American Society of Experimental Biology
• ISSN: 0892-6638
• ISSN (Online): 1530-6860
• Published Online: 05 February 2007