The influence of the neuropeptide galanin on the contractility and the effective refractory period of guinea-pig heart papillary muscle under normoxic and hypoxic conditions

The aim of this study was to discover the effects of galanin, a neuropeptid e comprising 29 amino acids capable of activating inward-rectifier K+ chann els (I-K1) in cardiomyocytes, on the force of contraction (Fc), velocity of contraction (+dF/dt), velocity of relaxation (-dF/dt) and effective refrac tory period (ERP) of guinea-pig heart. The influence of galanin on the time -course of hypoxia-induced disturbances in contractility and ERP was also e xamined. Experiments were performed on the isolated right ventricle papilla ry muscle of guinea-pig heart. In the concentration range 0.001-0.01 mu M, galanin had no significant effe ct on the measured parameters. At 0.03 and 0.1 mu M, galanin exerted a posi tive inotropic action and prolonged ERP. Further increasing the concentrati on led to a negative inotropic action and significant shortening of ERP. Al though simulated hypoxia induced a significant drop in Fc, +dF/dt and -dF/d t, and a significant shortening of ERP, recovery of all the measured parame ters was complete after 10 min reperfusion. In the presence of 0.03 and 0.1 mu M galanin the effect of hypoxia on the contractility of papillary muscl e was more profound and reperfusion did not result in complete recovery. In contrast, addition of 1 mu M galanin to the hypoxic solution significantly protected the muscle and recovery of the tissues during reperfusion was ra pid and complete (in 5 min). One can conclude that galanin at lower concentrations induced a positive in otropic action and a prolongation of ERP, but increased the sensitivity of heart muscle to hypoxia. At higher concentrations however, galanin exerted a negative inotropic action but protected the muscle against hypoxia-induce d disturbances in contractility.