Abstract

Objective: In diabetes mellitus several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models changes in these parameters were reported, but no such data are available in other mammalian species including the dog. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and its underlying transmembrane ionic currents and channel proteins in canine hearts. Methods and results: Diabetes was induced by a single injection of alloxan, a subgroup of dogs received insulin substitution. After the development of diabetes (8 weeks) electrophysiological studies were performed using conventional microelectrodes, whole cell voltage clamp, and ECG. Expression of ion channel proteins was evaluated by Western blotting. The QTc interval and the ventricular action potential duration in diabetic dogs were moderately prolonged. This was accompanied by significant reduction in the density of the transient outward K+ current (Ito) and the slow delayed rectifier K+ current (IKs), to 54.6% and 69.3% of control, respectively. No differences were observed in the density of the inward rectifier K+ current (IK1), rapid delayed rectifier K+ current (IKr), and L-type Ca2+ current (ICa). Western blot analysis revealed a reduced expression of Kv4.3 and MinK (to 25 ± 21% and 48 ± 15% of control, respectively) in diabetic dogs, while other channel proteins were unchanged (HERG, MiRP1, α1c) or increased (Kv1.4, KChIP2, KvLQT1). Insulin substitution fully prevented the diabetes-induced changes in IKs, KvLQT1 and MinK, however, the changes in Ito, Kv4.3, and Kv1.4 were only partially diminished by insulin. Conclusion: It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization, attenuates the repolarization reserve by decreasing Ito and IKs currents, and thereby may markedly enhance the risk of sudden cardiac death.

Original languageEnglish
Pages (from-to)512-520
Number of pages9
JournalCardiovascular research
Volume73
Issue number3
DOIs
Publication statusPublished - Feb 1 2007

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Keywords

  • Channel proteins
  • Diabetes mellitus
  • Potassium channels
  • QT interval
  • Repolarization reserve

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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