N-methyl-D-aspartate receptors in rat and human heart

The N-methyl-D-aspartate (NMDA) receptor is glutamate receptor that has been widely studied in central nervous system. It consists of 4 subunits that build ionotropic channel allowing ion flow through the cell membrane. Many studies showed the importance of NMDA receptors in the process of neurotransmission but few studies has been performed to evaluate the impact of receptors' function to cardiovascular system. The work presented in this doctoral thesis has been within the international joint research project established in 2012 between two scientific groups of Division of Cardiac Surgery, Department of Surgery at the University of Verona (Italy) and the Institute of Veterinary Physiology at the University of Zurich (Switzerland). The project focused on the role of receptors in healthy and diseased mammalian heart. The aims of current work were: • to perform a basic characterisation of the subunit composition of NMDA receptor; • to describe the distribution of the active receptors within the heart chambers of human and animal (rat); • to evaluate the role of these receptors in young and old rats; • to define if pathological remodelling of myocardium in human may be connected with cardiac receptors' properties. In the isolated blood perfused rat heart study evidenced the effect of intracoronary administration of agonists and antagonists of the NMDA receptors on electrical activity of myocardium. It has been shown that exposure to agonists provoke tachyarrhythmic reactions while antagonists produce mild bradycardia and stabilise the heart rhythm. In the study on the human heart it was observed that the expression of GluN2A and GluN2C subunits was significantly lower in patients with chronic atrial fibrillation rather than in patients with sinus rhythm.