Inhibiton of Protein Kinase G Preserves Prolonged Ventricular Action Potentials via Improvement of Slow-Activated Voltage-Dependent K+-Channel Currents in Aged Rat Cardiomyocytes

Abstract

Aging, being a complex process, is the most important risk factor for most diseases in humans giving a dominant risk factor for cardiovascularchanges. Aging, itself, does not cause heart failure among human, however it results in progressive deteriorations in the structure and function of the heart. Studies mentioned that carbohydrate intolerance develops as part of the aging process, being carbohydrate intolerance associated with the consequence of peripheral insulin resistance. However, there is an age-associated increase in the prevalence of abdominal obesity and insulin resistance in elderly subjects, with a clear relationship between metabolic syndrome and insulin resistance, while the percentage of QT-prolongation is high between elderly-subject comparison to adults at most due to depressed slow-activated voltage-dependent K+-channel currents (IKs), which is an indicator of an increased risk for potentially fatal cardiac arrhythmias. In the present study, we aimed to examine the underlying mechanism of aging-associated QT-prolongation in aged- and insulin resistant-rats. We emanined action potential parameters in left ventricular cardiomyocytes, under either insulin application or a IKs activator. Since we observed significantly activated PKG and positive response to insulin application in aged-rat cardiomyocytes,we also tested whether a PKG inhibitor can also induce recovery in the prolonged action potentials. Our all data demonstrated that the depressed IKs can play important role in aged-rat electrical activity via a activation of insulin resistant dependent activation of PKG. Theerfore, PKG seems to be a new target for the improvement of cardiac disorders during aging heart. (Supported by TUBITAK SBAG-216S979).