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Mechanical restitution in atrial muscle from human and rat hearts: effects of agents that modify sarcoplasmic
U Ravens1, J Gath, M al Hussaini
1Department of Pharmacology, University of Essen Medical School, Germany.
Abstract:
Force of contraction (Fc) of isolated human and rat atrial myocardium shows characteristic patterns of mechanical restitution when single test intervals are interposed in regular stimulation. With several pharmacological agents that modify the function of the sarcoplasmic reticulum we have investigated the role of the sarcoplasmic reticulum in mechanical 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 stimulate Ca2+ uptake. Under control conditions, Fc recovered rapidly with test intervals shorter than steady-state, and was potentiated with longer than steady-state intervals. In human atrial tissue the maximum potentiation factor was 1.26 +/- 0.03 after a mean test interval of 9.70 +/- 1.55 s (n = 43) as compared to 3.07 +/- 0.45 after 30 sec. in rat atria (n = 48). Caffeine (3 mM) did not significantly affect steady-state Fc but abolished post-rest potentiation in human and rat preparations. Forskolin (1 microM) enhanced and accentuated the mechanical restitution curve in particular for short test intervals. In the presence of thapsigargin (10 microM), steady-state Fc and mechanical restitution could not be distinguished from time-matched controls exposed to solvent only, indicating that this agent is ineffective in human and rat atrial tissue. In contrast, the putative Ca2+ uptake inhibitor BHQ (100 microM) strongly reduced steady-state Fc 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) induced post-rest decay in human and depressed both steady-state Fc 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.