The effects of potassium channel modulators on the simulated ischaemia-induced changes in contractility and responsiveness to phenylephrine of rat-isolated papillary muscle

The aim of the present study was to compare the influence of terikalant, a blocker of inwardly rectifying K+ channels, galanin, a neuropeptide of 29 aminoacids with a complex mechanism of action including an activation of inwardly rectifying K+ channels and glibenclamide, a blocker of ATP-sensitive K+ channels, on simulated ischaemia-induced changes in contractility and response to phenylephrine of rat-isolated heart muscle. Experiments were performed on isolated rat heart papillary muscles. The following parameters were measured: force of contraction (Fc), velocity of contraction (+dF/dt) and velocity of relaxation (-dF/dt), time to peak contraction (ttp) and relaxation time at 10% of total amplitude of contraction (tt(10)). In the presence of 1 mu M of galanin, as well as terikalant, simulated ischaemia caused a decrease in Fc, + dF/dt and -dF/dt, however, it significantly increased a drop in Pc and -dF/dt. After 60 min of reperfusion, all the measured parameters recovered completely except Fc in the galanin group. Terikalant, but not galanin, prevents the negative inotropic action of phenylephrine observed in the control group. On the other hand, addition of 1 mu M of glibenclamide to the no-substrate solution prevented the simulated ischaemia-induced decrease in Pc, + dF/dt and -dF/dt. In this group phenylephrine did not cause the negative inotropic action. The above mentioned data reveal that pretreatment with the inhibitors of ATP-sensitive and inwardly rectifying K+ channels protect rat-isolated papillary muscle against ischaemia-induced disturbances in contractility. (C) 1998 The Italian Pharmacological Society.