Trifluoperazine inhibition of contraction in permeabilized skeletal, cardiac and smooth muscles.
To gain insights into the mechanism of the central helix of calmodulin and troponin-C in the Ca2(+)-regulation of force development in striated and smooth muscles, the present study was made of the TFP induced inhibition of contraction, and of the uptake of these proteins by skinned fibers. Calmodulin was four-fold more sensitive to TFP than TnC, but the inhibition was found to be identical for skeletal and cardiac muscles despite the differences in their troponin-C isoforms. Also, the results were comparable between fast-twitch fiber, when calmodulin was exchanged for troponin-C to act on TnI, and smooth muscle, where calmodulin acts on myosin light chain kinase. These findings indicate that the inhibition of force by TFP is entirely due to its binding to the hydrophobic sites in the central helix. The uptakes of troponin-C and calmodulin were also different, and this is explained by a TFP-independent domain in troponin-C that binds TnI.
Babu
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A
Albert Einstein College of Medicine, Department of Medicine and Physiology/Biophysics, Bronx, NY 10461.
Gulati
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009132:Muscles / Q000187:drug effects / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects*; D011817:Rabbits; D012518:Sarcomeres / Q000187:drug effects / Q000502:physiology; D014268:Trifluoperazine / Q000494:pharmacology*; D014336:Troponin / Q000378:metabolism; D019209:Troponin C; D016276:Ventricular Function
D002147:Calmodulin; D014336:Troponin; D019209:Troponin C; D014268:Trifluoperazine; D002118:Calcium