Open AccessMechanical Restitution in Atrial Muscle from Human and Rat Hearts: Effects of Agents that Modify Sarcoplasmic Reticulum Function
Author(s) -
Ravens Ursula,
Gath Jennifer,
Hussaini Maryam Al,
Himmel Herbert
Publication year - 1997
Publication title -
pharmacology & toxicology
Language(s) - English
Resource type - Journals
eISSN - 1600-0773
pISSN - 0901-9928
DOI - 10.1111/j.1600-0773.1997.tb00038.x
Subject(s) - thapsigargin , endoplasmic reticulum , caffeine , ryanodine receptor , medicine , restitution , forskolin , endocrinology , chemistry , skeletal muscle , muscle contraction , stimulation , biology , biochemistry , political science , law
Force of contraction (F c ) 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)‐l,4‐benzohydroquinone (BHQ) were used to reduce Ca 2+ uptake, ryanodine to open Ca 2+ release channels, and forskolin to stimulate Ca 2+ uptake. Under control conditions, F c 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 F c but abolished post‐rest potentiation in human and rat preparations. Forskolin (1 μM) enhanced and accentuated the mechanical restitution curve in particular for short test intervals. In the presence of thapsigargin (10 μM), steady‐state F c 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 Ca 2+ uptake inhibitor BHQ (100 μM) 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) induced 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 Ca 2+ handling by the sarcoplasmic reticulum during mechanical restitution.