| First Author | Ufret-Vincenty CA | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 30 | Pages | 28197-203 |
| PubMed ID | 11369778 | Mgi Jnum | J:128830 |
| Mgi Id | MGI:3768062 | Doi | 10.1074/jbc.M102548200 |
| Citation | Ufret-Vincenty CA, et al. (2001) Role of sodium channel deglycosylation in the genesis of cardiac arrhythmias in heart failure. J Biol Chem 276(30):28197-203 |
| abstractText | 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. |
