MECHANICAL RESTITUTION IN ATRIAL MUSCLE FROM HUMAN AND RAT HEARTS - EFFECTS OF AGENTS THAT MODIFY SARCOPLASMIC-RETICULUM FUNCTION

Force of contraction (F-c) of isolated human and rat atrial myocardium shows characteristic patterns of mechanical restitution when single t est intervals are interposed in regular stimulation. With several phar macological agents that modify the function of the sarcoplasmic reticu lum we have investigated the role of the sarcoplasmic reticulum in mec hanical restitution in these two species. Caffeine, thapsigargin and 2 ,5-di-(tert-butyl)-1,4-benzohydroquinone (BHQ) were used to reduce Ca2 + uptake, ryanodine to open Ca2+ release channels, and forskolin to st imulate Ca2+ uptake. Under control conditions, F-c recovered rapidly w ith test intervals shorter than steady-stale, and was potentiated with longer than steady-state intervals. In human atrial tissue the maximu m potentiation factor was 1.26 +/- 0.03 after a mean lest interval of 9.70 +/- 1.55 s (n=43) as compared to 3.07 +/- 0.45 after 30 sec. in r at atria (n=48). Caffeine (3 mM) did not significantly affect steady-s tate F-c but abolished post-rest potentiation in human and rat prepara tions. Forskolin (1 mu M) enhanced and accentuated the mechanical rest itution curve in particular for short test intervals. In the presence of thapsigargin (10 mu M), steady-state F-c and mechanical restitution could not be distinguished from time-matched controls exposed to solv ent only, indicating that this agent is ineffective in human and rat a trial tissue. In contrast, the putative Ca2+ uptake inhibitor BHQ (100 mu M) strongly reduced steady-state F-c and decreased potentiation at all intervals in human muscle, but shifted the mechanical restitution curve in parallel to lower values in rat atria. Ryanodine (10 nM) ind uced post-rest decay in human and depressed both steady-state F-c and post-rest potentiation in rat atrial muscle. From these results it is concluded that human and rat atrial muscle differ in the Ca2+ handling by the sarcoplasmic reticulum during mechanical restitution.