The effect of acetylcholinesterase inhibition on preservation of connexin 43 degradation in cardomyocytes subjected to ischemia and ischemia/reperfusion condition

• Grant number: 15/08931-9
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: July 20, 2015
• End date: January 19, 2016
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rubens Fazan Junior
• Grantee: Fernanda Machado Santos de Almeida
• Supervisor: Henrique Manuel Paixão dos Santos Girão
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Universidade de Coimbra (UC), Portugal
• Associated to the scholarship: 13/26217-6 - Effect of acetylcholinesterase inhibition on connexin 43 preservation in the heart of rats with acute myocardial infarction, BP.PD

Abstract

The main cause of cardiac arrhythmias after acute myocardial infarction (AMI) is the electrical instability of cardiomyocyte membrane caused, among other causes, the deterioration of the protein responsible for maintaining the integrity of gap junctions present in the heart. The most important and abundant of these is the connexin 43 (Cx43). Evidences point out for an anti-arrhythmogenic role of cardiac vagal activity, since the use of parasympathomimetic agents or vagus electrical stimulation reduces the incidence of arrhythmias during acute myocardial infarction. Furthermore, it has been shown the correlation between cholinergic stimulation and prevention of heart Cx43 degradation in these conditions. Hence, we hypothesize that the anti-arrhythmogenic role of cardiac vagal stimulation has as background the preservation of gap junctions, mostly the protein Cx43. Nevertheless, it is unclear what the role of acetylcholine in Cx43 degradation pathways induced by cardiac tissue injury. Thus, this study aims to evaluate the effect of increasing the availability of acetylcholine by the administration of a parasympathomimetic agent, pyridostigmine bromide (PYR) on the amount and activity of proteins responsible for the degradation of Cx43, as Nedd4, p62, Eps15, AMPK and Beclin-1 in cardiomyocytes subjected to an ischemic medium during 4 hours and the ischemia followed by reperfusion. This work is part of the study conducted in Brazil that aims to evaluate the role of PYR in the incidence of cardiac arrhythmias and survival rates in rats after AMI (Process FAPESP2013 / 26217-6). (AU)