Differential effect of DPI 201-106 on the sensitivity of the myofilaments to Ca2+ in intact and skinned trabeculae from control and myopathic human hearts.
The effects of DPI, a new inotropic agent, were compared in trabeculae carneae from control and myopathic human hearts loaded with aequorin, a bioluminescent calcium indicator that emits light when it combines with calcium, and in saponin-skinned trabeculae carneae from the same hearts. The force-pCa curves in saponin-skinned fibers and the peak force-peak Ca2+ curves in aequorin-loaded preparations were not significantly different between the control and myopathic tissues. The force-pCa curve in the skinned and aequorin-loaded preparations from the same control hearts displayed no significant shifts with the addition of DPI. In contrast, a leftward shift was present in the force-calcium relationship in the presence of DPI in aequorin-loaded and skinned muscles from myopathic hearts, indicating an increase in the sensitivity of the myofilaments to calcium. These differences in the modulation of calcium activation between myopathic and control tissues indicate that pharmacological agents may produce differential effects in normal and diseased hearts.
Hajjar
R J
RJ
Massachusetts Institute of Technology, Division of Health Sciences and Technology, Cambridge 02139.
Gwathmey
J K
JK
Briggs
G M
GM
Morgan
J P
JP
D008841:Actin Cytoskeleton / Q000187:drug effects*; D000331:Aequorin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D009206:Myocardium / Q000648:ultrastructure*; D010879:Piperazines / Q000494:pharmacology*; D012503:Saponins
D010879:Piperazines; D012503:Saponins; D000331:Aequorin; C046261:DPI 201-106; D008274:Magnesium; D002118:Calcium