title: Thapsigargin inhibits the effects of noradrenaline and high [Ca2+]o on kinetics but not on amplitude of contraction in the single myocytes of guinea-pig heart.
abstract: We investigated the effect of selective blocker of Ca(2+)-ATPase of sarcoplasmic 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 changes 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 amplitude of contraction by 154 +/- 8%, decreased the time to peak contraction from 343 +/- 25 ms to 328 +/- 20 ms and decreased the total duration of contraction from 813 +/- 81 ms to 800 +/- 47 ms (not significant). The rate of rise of rapid phase of Ca2+ transients and their amplitude was increased and decay accelerated. The 10(-9) mM NA increased the amplitude of contraction by 154 +/- 9%, decreased time to peak contraction from 343 +/- 25 ms to 273 +/- 17 ms and the total duration of contraction from 813 +/- 81 ms to 603 +/- 28 ms. The rate of rise of the rapid phase of Ca2+ transients was greatly accelerated and their amplitude was increased. The 10(-7) M(TG) blocked completely the rapid phase of Ca2+ transients, increased time to peak [Ca2+]i and delayed decay. Total amplitude of the transients was hardly affected. Accordingly, time to peak contraction was prolonged to 583 +/- 50 ms but the amplitude of contraction was only slightly decreased. Calcium stores in the SR were completely depleted as assessed by caffeine Ca2+ transients and contractures. In the cells pretreated with TG 10(-9) M NA but not 5.0 mM Ca2+ increased amplitude of the transients. Amplitude of contractions was increased by both agents more than in the control cells. The 5.0 mM Ca2+ slightly decreased time to peak contraction and NA tended to increase it. Both inotropic agents accelerated relaxation. It is concluded that amplitude of contractions may be increased by stimulation of Ca2+ influx, however, the control of kinetics of contraction results from altered handling of the influx by the functioning SR.
authors.affiliation: Department of Clinical Physiology, Medical Center of Postgraduate Education, Warsaw, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Janiak
authors.forename: B
authors.initials: B
authors.lastname: Lewartowski
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009994:Osmolar Concentration; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin
chemical_list: D013729:Terpenes; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium; D009638:Norepinephrine