Cocaine enhances postrest and paired-stimulation potentiation in rat papillary muscle

We studied the effects of cocaine (20 mg/l; 58 microM) on paired-stimulation potentiation and rest-potentiation in isolated rat papillary muscles superfused with Tyrode's solution at 31 degrees C. A force transducer was used to measure peak tension developed, maximum velocity of development of tension and time to peak tension. The results show that, in preparations driven at a basic constant rate (0.5 Hz), cocaine had a depressant effect on peak tension developed and maximum velocity of development of tension and shortened time to peak tension. Propranolol or nifedipine did not modify the negative inotropic action of cocaine, whereas this action was blocked by caffeine. The results also show that cocaine enhanced rest-potentiation and paired-stimulation potentiation. In the presence of propranolol, the enhancement of paired-stimulation potentiation caused by cocaine remained intact, whereas it failed to do so under the influence of nifedipine. On the other hand, nifedipine did not affect the enhancing action of cocaine on rest-potentiation. Caffeine reversed both rest-potentiation and paired-stimulation potentiation; this action was not modified by cocaine. Thus, even though cocaine exerted a negative inotropic action on rat papillary muscles driven at a constant rate, it enhanced the potentiating action of maneuvers which modify the force-interval relation. Cocaine appears to cause these effects by acting at various levels of electro-mechanical coupling, such as the sarcolemma, the sarcoplasmic reticulum and the myofilaments sensitivity to calcium.