Different aspects of the effects of thapsigargin on automatism, contractility and responsiveness to phenylephrine in cardiac preparations from rats and guinea pigs.
Sarcoplasmic reticulum (SR) Ca(2+)-ATPase play a very important role in excitation-contraction coupling in the heart. The effects of thapsigargin (TG), a selective inhibitor of SR Ca(2+)-ATPase in the heart muscle, on automatism and contractility of the rat and guinea pig heart were examined. Experiments were performed on isolated right auricula and right ventricle papillary muscle. The following parameters were registered: force of contraction (Fc); rate of rise of force (+dF/dt); rate of fall of force (-dF/dt); time to peak contraction (ttp); duration of relaxation phase of contraction at the level of 10% of total amplitude (tt10); and automatism (b.p.m.). Additionally, the influence of thapsigargin on the effects of phenylephrine on the above mentioned parameters were studied. It was found that TG (1 microM) decreased only the automatism in rat heart, but increased automatism and ttp duration and decreased Fc in guinea pig heart. The positive force-frequency relation in the guinea pig heart was attenuated. The effects of phenylephrine in the rat heart were not significantly different before and after pretreatment with TG. Alternatively, pretreatment with TG exerted a profound influence on the effects of phenylephrine in the guinea pig heart. The results indicate that TG has different effects on the guinea pig and rat hearts. The reason for this could be due to species differences, i.e. the weaker crossing of TG through the membrane of rat myocytes or a different mechanism of Ca2+ homeostasis in rat and guinea pig hearts.
Kocic
I
I
Department of Pharmacology, Medical University of Gdañsk, Poland.
Dworakowska
D
D
Dworakowski
R
R
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D019284:Thapsigargin / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D010656:Phenylephrine; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases