Differential contribution of sialic acid to the function of repolarizing K+ currents in ventricular myocytes

Carmen A. Ufret-Vincenty, Deborah J. Baro, Luis Fernando Santana

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

We investigated the contribution of sialic acid residues to the K+ currents involved in the repolarization of mouse ventricular myocytes. Ventricular K+ currents had a rapidly inactivating component followed by slowly decaying and sustained components. This current was produced by the summation of three distinct currents: Ito, which contributed to the transient component; Iss, which contributed to the sustained component; and IK,slow, which contributed to both components. Incubation of ventricular myocytes with the sialidase neuraminidase reduced the amplitude of Ito without altering IK,slow and Iss. We found that the reduction in Ito amplitude resulted from a depolarizing shift in the voltage of activation and a reduction in the conductance of Ito. Expression of Kv4.3 channels, a major contributor to Ito in the ventricle, in a sialylation-deficient Chinese hamster ovary cell line (lec2) mimicked the effects of neuraminidase on the ventricular Ito. Furthermore, we showed that sialylated glycolipids have little effect on the voltage dependence of Ito. Finally, consistent with its actions on Ito, neuraminidase produced an increase in the duration of the action potential of ventricular myocytes and the frequency of early afterdepolarizations. We conclude that sialylation of the proteins forming Kv4 channels is important in determining the voltage dependence and conductance of Ito and that incomplete glycosylation of these channels could lead to arrhythmias.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume281
Issue number2 50-2
StatePublished - 2001
Externally publishedYes

Keywords

  • Arrhythmias
  • Glycosylation
  • Kv4.3
  • Mouse ventricular myocytes
  • Transient outward currents

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

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