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) Ca2+-ATPase plays a very important role in excitation-contraction coupling in the heart. The effects of thapsiga rgin (TG), a selective inhibitor of SR Ca2+-ATP-ase in the heart muscl e, on automatism and contractility of the rat and guinea pig heart wer e examined. Experiments were performed on isolated right auricula and right ventricle papillary muscle. The following parameters were regist ered: 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 amplitud e (tt(10)); and automatism (b.p.m.). Additionally, the influence of th apsigargin on the effects of phenylephrine on the above mentioned para meters were studied. It was found that TG (1 mu M) decreased only the automatism in rat heart, but increased automatism and ttp duration and decreased Fc in guinea pig heart. The positive force-frequency relati on in the guinea pig heart was attenuated. The effects of phenylephrin e in the rat heart were not significantly different before and after p retreatment with TG. Alternatively, pretreatment with TG exerted a pro found influence on the effects of phenylephrine in the guinea pig hear t. The results indicate that TG has different effects on the guinea pi g and rat hearts. The reason for this could be due to species differen ces, i.e. the weaker crossing of TG through the membrane of rat myocyt es or a different mechanism of Ca2+ homeostasis in rat and guinea pig hearts. (C) 1998 The Italian Pharmacological Society.