Effects of MCI-154 on Ca2+ activation of skinned human myocardium.
We investigated the effects of MCI-154, a new inotropic agent, on tension development in saponin-skinned human trabeculae carneae. The skinned fibers were activated by buffer solutions containing varying concentrations of Ca2+ (10(-8)-10(-4) M). In the sigmoidal tension vs. pCa (-log[Ca2+]M) relationship, the Ca2+ concentration required for half-maximal activation was shifted leftward in the presence of MCI-154. Furthermore, maximal Ca2+-activated tension development was increased in a concentration-dependent manner by MCI-154. Our results suggest that the inotropic effect of MCI-154 may be due, in part, to an increased sensitivity of the myofilaments to Ca2+ and enhancement of maximal Ca2+-activated tension development.
Charles A. Dana Research Institute, Beth Israel Hospital, Boston, MA 02215.
C L
CL
Perreault
F V
FV
Brozovich
B J
BJ
Ransil
J P
JP
Morgan
D002118:Calcium / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology*
D002316:Cardiotonic Agents; D011724:Pyridazines; C052228:MCI 154; D002118:Calcium