Effects of [Na+](o), [Ca2+](o) and cyclopiazonic acid on decline of post-extrasystolic potentiation and twitch kinetics in guinea-pig and human myocardial preparations

The decline of post-extrasystolic potentiation was investigated in atrial a nd Ventricular muscle of guinea-pigs and in human atrial muscle. This decli ne is described in terms of the recirculation fraction (RF) for calcium in myocardial cells. Under control conditions, the mean Values for RF were as follows: 0.61 +/- 0.03 in the guinea-pig atrium, 0.32 +/- 0.05 in the guine a-pig Ventricle and 0.51 +/- 0.10 in the human atrium. Upon increasing calc ium concentrations within the range of 0.5-10 mM or decreasing the sodium t o 70%, the steady-state force and recirculation fraction increased concomit antly in all three types of muscles. Cyclopiazonic acid (CPA), in a 5-20 mu M concentration, decreased force in the guinea-pig preparations and decrea sed RF. The effects of CPA were great in atrial muscle, 20 mu M CPA decreas ing RF from 0.61 to 0.39. In ventricular muscle, this effect was small and not statistically significant When changing calcium or sodium concentration s, increased force was accompanied by slower relaxation in atrial muscle, b ut an unchanged or slightly faster relaxation in ventricular muscle. In gui nea-pig myocardium, CPA (5-20 mu M) prolonged the lime to peak force (TPF), but it slowed relaxation only in the ventricle. Reducing the calcium outfl ow by Na/Ca exchange increased RF as expected, and reducing the SR calcium re-uptake decreased RF. These interventions were also expected to reduce th e rate of decline of intracellular calcium, but relaxation was not consiste ntly prolonged. This indicates that factors other than the SR calcium pump and sarcolemmal Na/Ca exchange determine, or at least influence, the rate o f relaxation.