Diabetes mellitus attenuates the repolarization reserve in mammalian heart
| Autor: | Miklós Tóth, Erzsébet Kocsis, László Virág, Péter P. Nánási, Csaba Lengyel, Peter Biliczki, Norbert Jost, András Varró, Valéria Kecskeméti, Réka Skoumal, Julius Gyula Papp, Tamás Bíró, János Magyar |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Patch-Clamp Techniques Calcium Channels L-Type Physiology Voltage clamp medicine.medical_treatment hERG Blotting Western Action Potentials Diabetes Mellitus Experimental Electrocardiography Dogs Physiology (medical) Internal medicine Diabetes mellitus medicine Repolarization Animals Insulin KvLQT1 Elméleti orvostudományok Potassium Channels Inwardly Rectifying Type 1 diabetes biology business.industry Myocardium Orvostudományok medicine.disease Potassium channel Endocrinology Diabetes Mellitus Type 1 Shal Potassium Channels KCNQ1 Potassium Channel biology.protein Kv1.4 Potassium Channel Female Cardiology and Cardiovascular Medicine business Delayed Rectifier Potassium Channels |
| Popis: | 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, andECG.ExpressionofionchannelproteinswasevaluatedbyWesternblotting.TheQTcintervalandtheventricularactionpotentialdurationin diabetic dogs were moderately prolonged. This was accompanied by significant reduction in the density ofthe 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 Ca 2+ 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. © 2006 European Society of Cardiology. Published by Elsevier B.V. |
| Databáze: | OpenAIRE |
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