MECHANISMS UNDERLYING THE GENESIS OF POSTEXTRASYSTOLIC POTENTIATION IN RAT CARDIAC-MUSCLE

Changes of contractility resulting from changes in stimulation pattern (post-extrasystolic potentiation - PESP) were investigated in right v entricular papillary muscles from female albino rats (EPM strain, 160- 200 g). The preparations were superfused with bicarbonate buffered sol ution at 24 +/- 0.5 degrees C, and stimulated at 0.5 Hz. Maintained pa ired stimulation was performed at several coupling intervals (360, 500 , 660, 770 and 920 ms) with normal Krebs for 30 s. After treatment wit h ryanodine (1 mu M), used as an inhibitor of the release of sarcoplas mic reticulum Ca2+ activity, the same protocol was repeated in the pre sence of normal Krebs, low Na+ (80 mM, LiCl used as substitute) and lo w K+ concentrations to change the level of activity of the Na+/Ca2+ ex change mechanism. With normal Krebs, paired pulse stimulation produced a maintained potentiation of the post-extrasystolic beat and an extra systole with a reduced force generation when compared to the control s teady-state contraction. As the interval between the extrasystole and the normal beat was increased the potentiation of the post-extrasystol ic beat was reduced and the force of the extrasystole was increased. R yanodine treatment reduced the force of contraction and increased its duration, and the pattern of the PESP phenomenon was altered. Both the post-extrasystolic and the extrasystolic beats were potentiated compa red to the steady-state contraction obtained under ryanodine treatment . The extrasystole displayed a greater potentiation than the post-extr asystolic beat. As the interval between them increased the amplitude o f the extrasystolic beat was enhanced. The differences in peak force b etween the extrasystolic and the post-extrasystolic beats were almost abolished during the treatment with ryanodine and at low extracellular Na+ concentration. This maneuver decreases the intracellular Na+ enha ncing Ca2+ extrusion by the Na+/Ca2+ exchanger. The resulting intracel lular Ca2+ reduction decreases peak force and the differences between the extrasystolic and the post-extrasystolic beats. The low K+ concent ration enhanced the pattern displayed after ryanodine treatment at nor mal K+ concentration. It may be concluded that the characteristics of the potentiation phenomenon promoted by the paired stimulation under c ontrol conditions depend on the activities of the sarcoplasmic reticul um and of the Na+/Ca2+ exchange mechanism.