DITPA restores the repolarizing potassium currents Itof and Iss in cardiac ventricular myocytes of diabetic rats
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- 作者：Tania Ferrer ; Mó ; nica Gallego ; Rafael Madrigal-Quiñ ; ó ; nez ; Juliá ; n Torres-Já ; come ; Ricardo Navarro-Polanco ; Oscar Cá ; sis and José ; A. Sá ; nchez-Chapula
- 关键词：Electrophysiology ; Ito ; Regulation ; Diabetes ; Hypothyroidism
- 刊名：Life Sciences
- 出版年：2006
- 出版时间：24 July 2006
- 年：2006
- 卷：79
- 期：9
- 页码：883-889
- 全文大小：213 K
文摘
Diabetes Mellitus (DM) can produce an increase in the cardiac action potential duration and QT interval that can be associated with sudden death. These cardiac effects are due to a region-specific decrease in repolarizing outward K+ currents. Some authors have suggested that the proarrhythmic effects of diabetes can be due to diabetes-induced hypothyroidism. Thus, we have examined the effect of the thyroid hormone analog diiodothyropropionic acid (DITPA) on calcium-independent outward potassium currents in ventricular myocytes from diabetic rats. Sustained (Iss) and fast transient outward (Itof) K+ currents were recorded using the whole-cell configuration of the patch-clamp technique. Myocytes were enzymatically isolated from the free wall of the right ventricle, and the epicardial and endocardial layers of the left ventricle of healthy, diabetic and DITPA-treated diabetic rats. Circulating thyroid hormones were measured by electrochemiluminescence. DITPA-treatment of diabetic rats restored Itof and Iss current densities in cardiac myocytes from the three regions studied, but did not alter current densities in myocytes of control rats. T3 and T4 levels were reduced by diabetes, and DITPA-treatment increased circulating T3 levels. T3-treatment of diabetic rats also restored current densities to control values. However, direct incubation of diabetic myocytes with DITPA did not restore current densities. In summary, DITPA-treatment of diabetic rats restored the potassium current (Itof and Iss) densities in myocytes from all ventricular regions.