Contractile properties of single muscle fibers in myotonic dystrophy

Muscle fiber contractile dysfunction in myotonic dystrophy (MD) is poorly u nderstood. We biopsied the tibialis anterior of two symptomatic and three a symptomatic subjects (aged 21-31 years) with the MD mutation. Biopsies were freeze dried. A total of 103 single muscle fibers were activated with Ca+, allowing maximal force measurements and specific force (SF) estimates. Th e slack test was performed to calculate maximum unloaded shortening velocit y (V-o). The myosin heavy chain composition of each fiber was determined us ing sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), Type I and IIA fibers of all subjects had reduced SF when compared with hea lthy control subjects (Pi 0.001). In addition, the type I fibers of symptom atic subjects generated less SF than those of asymptomatic subjects (P < 0. 001). Type I fibers from asymptomatic and symptomatic subjects did not diff er in V-o, but V-o was lower than in control subjects (P < 0.001). There wa s no significant difference in V-o of type IIA fibers from symptomatic, asy mptomatic, and control subjects. These results indicate that the MD mutatio n leads to a diminished force-generating capacity of the myofilaments in bo th symptomatic acid asymptomatic individuals. The results further suggest t hat reduction in force-generating capacity at the cellular level develops p rior to clinical weakness. (C) 2000 John Wiley & Sons, Inc.