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Role of sodium channel deglycosylation in the genesis of cardiac arrhythmias in heart failure.

Publication ,  Journal Article
Ufret-Vincenty, CA; Baro, DJ; Lederer, WJ; Rockman, HA; Quinones, LE; Santana, LF
Published in: J Biol Chem
July 27, 2001

We investigated the cellular and molecular mechanisms underlying arrhythmias in heart failure. A genetically engineered mouse lacking the expression of the muscle LIM protein (MLP-/-) was used in this study as a model of heart failure. We used electrocardiography and patch clamp techniques to examine the electrophysiological properties of MLP-/- hearts. We found that MLP-/- myocytes had smaller Na+ currents with altered voltage dependencies of activation and inactivation and slower rates of inactivation than control myocytes. These changes in Na+ currents contributed to longer action potentials and to a higher probability of early afterdepolarizations in MLP-/- than in control myocytes. Western blot analysis suggested that the smaller Na+ current in MLP-/- myocytes resulted from a reduction in Na+ channel protein. Interestingly, the blots also revealed that the alpha-subunit of the Na+ channel from the MLP-/- heart had a lower average molecular weight than in the control heart. Treating control myocytes with the sialidase neuraminidase mimicked the changes in voltage dependence and rate of inactivation of Na+ currents observed in MLP-/- myocytes. Neuraminidase had no effect on MLP-/- cells thus suggesting that Na+ channels in these cells were sialic acid-deficient. We conclude that deficient glycosylation of Na+ channel contributes to Na+ current-dependent arrhythmogenesis in heart failure.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 27, 2001

Volume

276

Issue

30

Start / End Page

28197 / 28203

Location

United States

Related Subject Headings

  • Sodium Channels
  • Sodium
  • Protein Processing, Post-Translational
  • Patch-Clamp Techniques
  • Neuraminidase
  • Mice, Transgenic
  • Mice
  • Humans
  • Heart Failure
  • Glycosylation
 

Citation

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Ufret-Vincenty, C. A., Baro, D. J., Lederer, W. J., Rockman, H. A., Quinones, L. E., & Santana, L. F. (2001). Role of sodium channel deglycosylation in the genesis of cardiac arrhythmias in heart failure. J Biol Chem, 276(30), 28197–28203. https://doi.org/10.1074/jbc.M102548200
Ufret-Vincenty, C. A., D. J. Baro, W. J. Lederer, H. A. Rockman, L. E. Quinones, and L. F. Santana. “Role of sodium channel deglycosylation in the genesis of cardiac arrhythmias in heart failure.J Biol Chem 276, no. 30 (July 27, 2001): 28197–203. https://doi.org/10.1074/jbc.M102548200.
Ufret-Vincenty CA, Baro DJ, Lederer WJ, Rockman HA, Quinones LE, Santana LF. Role of sodium channel deglycosylation in the genesis of cardiac arrhythmias in heart failure. J Biol Chem. 2001 Jul 27;276(30):28197–203.
Ufret-Vincenty, C. A., et al. “Role of sodium channel deglycosylation in the genesis of cardiac arrhythmias in heart failure.J Biol Chem, vol. 276, no. 30, July 2001, pp. 28197–203. Pubmed, doi:10.1074/jbc.M102548200.
Ufret-Vincenty CA, Baro DJ, Lederer WJ, Rockman HA, Quinones LE, Santana LF. Role of sodium channel deglycosylation in the genesis of cardiac arrhythmias in heart failure. J Biol Chem. 2001 Jul 27;276(30):28197–28203.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 27, 2001

Volume

276

Issue

30

Start / End Page

28197 / 28203

Location

United States

Related Subject Headings

  • Sodium Channels
  • Sodium
  • Protein Processing, Post-Translational
  • Patch-Clamp Techniques
  • Neuraminidase
  • Mice, Transgenic
  • Mice
  • Humans
  • Heart Failure
  • Glycosylation