Improvement of the metabolic status recovers cardiac potassium channel synthesis in experimental diabetes. (27th December 2012)

• Record Type: Journal Article
• Authors: Torres‐Jacome, J.; Gallego, M.; Rodríguez‐Robledo, J. M.; Sanchez‐Chapula, J. A.; Casis, O.
• Is Part Of: Acta physiologica. Volume 207:Number 3(2013:Mar.)
• Page Start: 447
• Page End: 459
• Publication Date: 2012-12-27
• Subjects: Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.12043
• Languages: English
• ISSNs: 1748-1708

Abstract

<abstract abstract-type="main" id="apha12043-abs-0001"> <title>Abstract</title> <sec id="apha12043-sec-0001" sec-type="section"> <title>Aims</title> <p>The fast transient outward current, <italic>I</italic><sub>to, fast</sub>, is the most extensively studied cardiac K<sup>+</sup> current in diabetic animals. Two hypotheses have been proposed to explain how type‐1 diabetes reduces this current in cardiac muscle. The first one is a deficiency in channel expression due to a defect in the trophic effect of insulin. The second one proposes flawed glucose metabolism as the cause of the reduced <italic>I</italic><sub>to, fast</sub>. Moreover, little information exists about the effects and possible mechanisms of diabetes on the other repolarizing currents of the human heart: <italic>I</italic><sub>to, slow</sub>, <italic>I</italic><sub>Kr</sub>, <italic>I</italic><sub>Ks</sub>, <italic>I</italic><sub>Kur</sub>, <italic>I</italic><sub>Kslow</sub> and <italic>I</italic><sub>K1</sub>.</p> </sec> <sec id="apha12043-sec-0002" sec-type="section"> <title>Methods</title> <p>We recorded cardiac action potentials and K<sup>+</sup> currents in ventricular cells isolated from control and streptozotocin‐ or alloxan‐induced diabetic mice and rabbits. Channel protein expression was determined by immunofluorescence.</p> </sec> <sec id="apha12043-sec-0003" sec-type="section"> <title>Results</title> <p>Diabetes reduces the amplitude of <italic>I</italic><sub>to, fast</sub>, <italic>I</italic><sub>to, slow</sub> and <italic>I</italic><sub>Kslow</sub>, in ventricular myocytes from mouse and rabbit, with no effect on <italic>I</italic><sub>ss</sub>, <italic>I</italic><sub>Kr</sub> or <italic>I</italic><sub>K1</sub>. The absence of changes in the biophysical properties of the currents and the immunofluorescence experiments confirmed the reduction in channel protein synthesis. Six‐hour incubation of myocytes with insulin or pyruvate recovered current amplitudes and fluorescent staining. The activation of AMP‐K reduced the same K<sup>+</sup> currents in healthy myocytes and prevented the pyruvate‐induced current recovery.</p> </sec> <sec id="apha12043-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Diabetes reduces K<sup>+</sup> current densities in ventricular myocytes due to a defect in channel protein synthesis. Activation of AMP‐K secondary to deterioration in the metabolic status of the cells is responsible for K<sup>+</sup> channel reductions.</p> </sec> </abstract>