ECCENTRIC CONTRACTION-INDUCED INJURY OF MOUSE SOLEUS MUSCLE - EFFECT OF VARYING [CA2+](O)

The objective of this study was to determine the effect of varying ext racellular Ca2+ concentration (Ca2+(o)) on eccentric contraction-ind uced muscle injury. Isolated mouse soleus muscles (n = 64) performed e ither 20 eccentric or 20 isometric contractions over a 40-min period i n a Krebs buffer containing 0.5, 1.25, or 5.0 mM Ca2+. Measurements of contractile function and lactate dehydrogenase accumulation in the bu ffer were then made every 15 min for 2 h. Prostaglandin E(2), leukotri ene B-4, and tyrosine accumulation in the incubation medium and total muscle Ca2+ were measured at the end of the experiment. Reductions i n maximal isometric tetanic force for muscles immediately after perfor mance of 20 eccentric and 20 isometric contractions were 21.1 +/- 1.4 and 1.2 +/- 0.7%, respectively. Total muscle Ca2+ was 28-37% higher in muscles that performed eccentric contractions than in those that pe rformed isometric contractions. However, estimates made with a confoca l laser scanning microscope and fluo 3 do not indicate that there was a difference in free cytosolic Ca2+ between fibers from injured and control muscles. Also, leukotriene B-4, prostaglandin E(2), and tyrosi ne accumulation in the buffer from muscles that performed eccentric co ntractions was not elevated over that from muscles that performed isom etric contractions. Furthermore, lactate dehydrogenase accumulation an d reductions of contractile function over the 2-h incubation period we re not enhanced by higher Ca2+(o) or influenced by the type of contr action. These findings suggest that muscles that were injured by eccen tric contractions were able to buffer the increased influx of extracel lular Ca2+, maintain a normal free cytosolic Ca2+, and avoid activat ion of Ca2+-sensitive degradative pathways.