Sarcomere Dynamics During Contraction-Induced Injury to Permeabilized Single Muscle Fibers.

Abstract

A contraction-induced injury results when an activated skeletal muscle or a single fiber is stretched in a ‘lengthening contraction’. This type of injury to muscle fibers is a leading cause of the loss of mobility that is associated with old age. Manifestations of the injury revealed by electron microscopy show focally disrupted single sarcomeres, or small groups of sarcomeres, that are surrounded by intact sarcomeres. The purpose of this dissertation was to study the dynamic behavior of sarcomeres during lengthening contractions of single muscle fibers. The working hypothesis was that contraction-induced injury occurs during a lengthening contraction when sarcomeres undergo elongation at varying rates and those lengthened at the highest rates reach longer lengths and are damaged. To test this hypothesis, a laser scanning system was developed that recorded rapidly (500 s−1) the lengths of sarcomeres contained in each of 20 contiguous regions along ~1 mm segments of a fiber. The fiber segments were obtained from soleus muscles of adult male rats and the membranes of the fibers were permeabilized chemically. The experiments performed with the laser scanning apparatus, indicated that: (i) during a lengthening contraction, the regions of fibers that contain the longer sarcomeres at the onset of the lengthening elongate more compared with the regions that contain shorter sarcomeres; (ii) lengthening contractions increased the variability in the lengths of sarcomeres in relaxed fibers; and (iii) during a lengthening contraction, within any given fiber region, the rate of elongation of sarcomeres was stable, but different regions stretched at different rates as the contraction proceeded. The present findings support the hypothesis that, within single fibers, non-uniformities develop in the lengths of sarcomeres that are increased by a lengthening contraction. The finding that all fiber regions elongate at stable rates during lengthening contractions contradicts a previous hypothesis that during lengthening contractions, the longest sarcomeres undergo rapid and sudden elongation to extreme lengths. The conclusion is that during lengthening contractions, the longer sarcomeres in series with shorter sarcomeres undergo elongation at higher velocities and upon return to original length, structural elements within some of these longer sarcomeres are functionally compromised.