Effects of amrinone on shortening velocity and force development in skinned skeletal muscle fibres

R. Aottinelli, V. Cappelli, S. E J N Morner, C. Reggiani

Research output: Contribution to journalArticle

Abstract

The effects of amrinone were studied on single skinned fibres isolated from rat hindlimb muscles. In each fibre a force-velocity relation was determined during maximal calcium activation (pCa=4.45) in control conditions and in the presence of amrinone. The MgATP concentration was 3.93 m m, close to the physiological value. After the experiment the fibre was classified as fast or slow on the basis of its reactivity with anti-myosin monoclonal antibodies. In fast fibres amrinone (3 m m) potentiated isometric tension (P0) by 13.8±2.9% (n=13), reduced maximum shortening velocity (Vmax) by 32.6±3.2% and the curvature of the force-velocity relation (a/P0) was increased by 98.9±46.0%. All these effects were less pronounced in slow fibres, where Vmax was reduced only by 11.4±3.6 (n=16). The effects of amrinone (0.3-6 m m) on the ATPase activity of myofibrils and myosin prepared from fast (tibialis anterior) and slow (soleus) rat skeletal muscles were studied. Amrinone was found to depress Ca-Mg dependent ATPase activity of myofibrillar preparations of the tibialis anterior (up to 16.6±2%) and, to a lesser extent, of the soleus (up to 7.2±1.2%). On the contrary, Ca-stimulated myosin ATPase activity was significantly increased by amrinone in myosin preparations from the tibialis anterior. Experiments were carried out to test whether amrinone (3 m m) might affect the sensitivity of the contractile system to MgATP concentration ([MgATP]). The results obtained showed that (1) the [MgATP] value at which isometric tension reached its maximum was shifted by amrinone from 0.1 m m to 0.3 m m, (2) the slope of the negative relation between [MgATP] and a/P0 was made more steep by amrinone, and (3) the Km of the hyperbolic relation between [MgATP] and Vmax was increased from 0.39 to 1.71 m m by amrinone, thus indicating a reduced affinity of myosin for MgATP. These results are in accordance with the hypothesis that amrinone exerts a direct effect on the contractile mechanism.

Original languageEnglish
Pages (from-to)110-120
Number of pages11
JournalJournal of Muscle Research and Cell Motility
Volume14
Issue number1
DOIs
Publication statusPublished - Feb 1993

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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