Effect of a cardiotonic agent, MCI-154, on the contractile properties of skinned skeletal muscle fibers

European Journal of Pharmacology
Hiroyuki Iwamoto

Abstract

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.

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Citations

Apr 17, 2002·Journal of Molecular Biology·Hiroyuki IwamotoTetsuro Fujisawa
Jul 11, 2008·Journal of Muscle Research and Cell Motility·Hiroyuki Iwamoto
May 18, 2004·Biochemical and Biophysical Research Communications·Takumi Tamura, Hiroyuki Iwamoto

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