Role of sodium channel deglycosylation in the genesis of cardiac arrhythmias in heart failure.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Ufret-Vincenty, CA; Baro, DJ; Lederer, WJ; Rockman, HA; Quinones, LE; Santana, LF
Published Date
- July 27, 2001
Published In
Volume / Issue
- 276 / 30
Start / End Page
- 28197 - 28203
PubMed ID
- 11369778
International Standard Serial Number (ISSN)
- 0021-9258
Digital Object Identifier (DOI)
- 10.1074/jbc.M102548200
Language
- eng
Conference Location
- United States