Modulatory role of sigma signalling in electromechanical coupling of isolated cardiomyocyte and heart
The proposed project deals with the role of sigma receptors in mammalian myocardium. The experiments are designed to answer some elementary questions concerning the effect of sigma signallingt on electromechanical coupling in rat, guinea pig and rabbit heart. Since the effect of sigma receptor binding has been previously studied mainly in rat ventricular cardiomyocytes, it is necessary to extend the experiments also to isolated heart and multicellular heart preparation and to other species. The project is focused on detailed analysis of electrical and mechanical consequences of sigma receptor binding in mammalian myocardium, with respect to differences between species and differences between preparations used (isolated cardiomyocytes, multicellular heart preparations, isolted heart). To study electrophysiological effects of sigma ligands in heart muscle voltage clamp and patch clamp techniqes will be used. Moreover, recording of monophasic action potentials by voltage sensitive dyes will be employed. Mechanical properties of cardiac muscle will be studied by analyses of left ventricular pressure curves and mechanograms from multicellular heart preparations. Putative cytotoxic effects of sigma ligands will be studied in morphological part of the project using electron microschopy techniques. The expected contribution of this project is obtaining of the electrophysiological correlates to inotropic action of sigma receptors and mapping differences between species.
Total number of publications: 30