Effect of a cardiotonic agent, MCI-154, on the contractile properties of skinned skeletal muscle fibers.
We have studied the effect of a cardiotonic agent, MCI-154 (6-[4-(4-pyridylamino)phenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride trihydrate), on the contractile properties and adenosine triphosphatase (ATPase) activity of chemically skinned rabbit skeletal muscle fibers. As in cardiac muscle, MCI-154 potentiated isometric tension and improved isometric tension cost at full Ca2+ activation. It showed little Ca2+-sensitizing effect. In contrast to its effect on cardiac muscle, however, MCI-154 decreased all the kinetic parameters tested (shortening velocity, the rate of rise of tension, and actomyosin ATPase activity). All the results are explainable if MCI-154 acts directly on skeletal actomyosin and inhibits a reaction step(s) of the ATPase cycle later than the force-generating event. The qualitative difference between cardiac and skeletal muscles in the responsiveness to this class of cardiotonic agents (MCI-154 and EMD 53998, a thiadiazinone derivative) is most readily understood if the agents have two independent actions, one on troponin and the other on actomyosin itself, the latter being dominant in skeletal muscle.
Iwamoto
H
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Department of Physiology, School of Medicine, Teikyo University, Tokyo, Japan. iwamoto@spring8.or.jp
D000251:Adenosine Triphosphatases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism; D007537:Isometric Contraction / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000201:enzymology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D010710:Phosphates / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D011817:Rabbits
D002316:Cardiotonic Agents; D010710:Phosphates; D011724:Pyridazines; C052228:MCI 154; D003402:Creatine Kinase; D000251:Adenosine Triphosphatases