THAPSIGARGIN INHIBITS THE EFFECTS OF NORADRENALINE AND HIGH [CA2-PIG HEART(](0) ON KINETICS BUT NOT ON AMPLITUDE OF CONTRACTION IN THE SINGLE MYOCYTES OF GUINEA)

We investigated the effect of selective blocker of Ca2+-ATPase of sarc oplasmic reticulum (SR), thapsigargin (TG), on the responses of single myocytes of guinea-pig heart to high [Ca2+](o) and noradrenaline (NA) . The cells were loaded with acetomethylester of Indo 1 and free [Ca2](i) monitored as the ratio of fluorescence at 405 and 495 nm. The cha nges in cell length were monitored by a TV displacement system. In the normal cells increase in [Ca2+](o) from 2.0 to 5.0 mM increased ampli tude of contraction by 154 +/- 8%, decreased the time to peak contract ion from 343 +/- 25 ms to 328 +/- 20 ms and decreased the total durati on of contraction from 813 +/- 81 ms to 800 +/- 47 ms (not significant ). The rate of rise of rapid phase of Ca2+ transients and their amplit ude was increased and decay accelerated. The 10(-9) mM NA increased th e amplitude of contraction by 154 +/- 9%, decreased time to peak contr action from 343 +/- 25 ms to 273 +/- 17 ms and the total duration of c ontraction from 813 +/- 81 ms to 603 +/- 28 ms. The rate of rise of th e rapid phase of Ca2+ transients was greatly accelerated and their amp litude was increased. The 10(-7) M(TG) blocked completely the rapid ph ase of Ca2+ transients, increased time to peak [Ca2+](i) and delayed d ecay. Total amplitude of the transients was hardly affected. According ly, time to peak contraction was prolonged to 583 +/- 50 ms but the am plitude of contraction was only slightly decreased. Calcium stores in the SR were completely depleted as assessed by caffeine Ca2+ transient s and contractures. In the cells pretreated with TG 10(-9) M NA but no t 5.0 mM Ca2+ increased amplitude of the transients. Amplitude of cont ractions was increased by both agents more than in the control cells. The 5.0 mM Ca2+ slightly decreased time to peak contraction and NA ten ded to increase it. Both inotropic agents accelerated relaxation. It i s concluded that amplitude of contractions may be increased by stimula tion of Ca2+ influx, however, the control of kinetics of contraction r esults from altered handling of the influx by the functioning SR.