REAL

Diabetes mellitus attenuates the repolarization reserve in mammalian heart

Lengyel, Csaba Attila and Virág, László and Bíró, Tamás and Jost, Norbert and Magyar, János and Biliczki, Péter and Kocsis, Erzsébet and Skoumal, Réka and Nánási, Péter Pál and Tóth, Miklós and Kecskeméti, Valéria and Papp, Julius Gyula and Varró, András (2007) Diabetes mellitus attenuates the repolarization reserve in mammalian heart. Cardiovascular Research, 73 (3). pp. 512-520. ISSN 0008-6363 (print), 1755-3245 (online)

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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 I 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 QT(c) 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 (I-to) and the slow delayed rectifier K+ current (I-Ks), to 54.6% and 69.3% of control, respectively. No differences were observed in the density of the inward rectifier K+ current (I-K1), rapid delayed rectifier K+ current (I-Kr), and L-type Ca2+ current (I-Ca). 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, alpha(1c)) or increased (Kv1.4, KChIP2, KvLQT1). Insulin substitution fully prevented the diabetes-induced changes in I-Ks, KvLQT1 and MinK, however, the changes in I-to, Kv4.3, and Kv1.4 were only partially diminished by insulin. Conclusion: It is concluded that type I diabetes mellitus, although only moderately, lengthens ventricular repolarization, attenuates the repolarization reserve by decreasing I-to and I-Ks currents, and thereby may markedly enhance the risk of sudden cardiac death.

Item Type: Article
Subjects: R Medicine / orvostudomány > RZ Other systems of medicine / orvostudomány egyéb területei
Depositing User: Erika Bilicsi
Date Deposited: 11 Mar 2013 15:20
Last Modified: 11 Mar 2013 15:20
URI: http://real.mtak.hu/id/eprint/4387

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