Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart

Cs Lengyel, L. Virág, P. P. Kovács, A. Kristóf, P. Pacher, E. Kocsis, Zs M. Koltay, P. P. Nánási, M. Tóth, V. Kecskeméti, J. Gy Papp, A. Varró, N. Jost

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Abstract

Aim: In diabetes mellitus, several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models, changes in these parameters were reported, but only limited relevant information is available in other species, having cardiac electrophysiological properties more resembling the human, including the rabbit. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and the underlying transmembrane potassium currents in rabbit hearts. Methods: Diabetes was induced by a single injection of alloxan (145 mg kg-1 i.v.). After the development of diabetes (3 weeks), electrophysiological studies were performed using whole cell voltage clamp and ECG measurements. Results: The QTc interval in diabetic rabbits was moderately but statistically significantly longer than measured in the control animals (155 ± 1.8 ms vs. 145 ± 2.8 ms, respectively, n = 9-10, P < 0.05). This QTc-lengthening effect of diabetes was accompanied by a significant reduction in the density of the slow delayed rectifier K + current, IKs (from 1.48 ± 0.35 to 0.86 ± 0.17 pA pF-1 at +50 mV, n = 19-21, P < 0.05) without changes in current kinetics. No differences were observed either in the density or in the kinetics of the inward rectifier K+ current (IK1), the rapid delayed rectifier K+ current (IKr), the transient outward current (Ito) and the L-type calcium current (I CaL) between the control and alloxan-treated rabbits. Conclusion: It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization. Diabetes attenuates the repolarization reserve by decreasing the density of IKs current, and thereby may enhance the risk of sudden cardiac death.

Original languageEnglish
Pages (from-to)359-368
Number of pages10
JournalActa Physiologica
Volume192
Issue number3
DOIs
Publication statusPublished - Mar 1 2008

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Keywords

  • Alloxan
  • Diabetes mellitus
  • Heart
  • Potassium channels
  • QT interval
  • Rabbit
  • Repolarization reserve

ASJC Scopus subject areas

  • Physiology

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