THE EFFECTS OF POTASSIUM CHANNEL MODULATORS ON THE SIMULATED ISCHEMIA-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 terikalan t, a blocker of inwardly rectifying K+ channels, galanin, a neuropepti de of 29 aminoacids with a complex mechanism of action including an ac tivation of inwardly rectifying K+ channels and glibenclamide, a block er of ATP-sensitive K+ channels, on simulated ischaemia-induced change s in contractility and response to phenylephrine of rat-isolated heart muscle. Experiments were performed on isolated rat heart papillary mu scles. The following parameters were measured: force of contraction (F c), velocity of contraction (+dF/dt) and velocity of relaxation (-dF/d t), 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 galan in, 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 n ot galanin, prevents the negative inotropic action of phenylephrine ob served in the control group. On the other hand, addition of 1 mu M of glibenclamide to the no-substrate solution prevented the simulated isc haemia-induced decrease in Pc, + dF/dt and -dF/dt. In this group pheny lephrine did not cause the negative inotropic action. The above mentio ned data reveal that pretreatment with the inhibitors of ATP-sensitive and inwardly rectifying K+ channels protect rat-isolated papillary mu scle against ischaemia-induced disturbances in contractility. (C) 1998 The Italian Pharmacological Society.