Contractile properties of single muscle fibers in myotonic dystrophy

Abstract

Muscle fiber contractile dysfunction in myotonic dystrophy (MD) is poorly understood. We biopsied the tibialis anterior of two symptomatic and three asymptomatic 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. The slack test was performed to calculate maximum unloaded shortening velocity (Vo). The myosin heavy chain composition of each fiber was determined using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Type I and IIA fibers of all subjects had reduced SF when compared with healthy control subjects (P < 0.001). In addition, the type I fibers of symptomatic subjects generated less SF than those of asymptomatic subjects (P < 0.001). Type I fibers from asymptomatic and symptomatic subjects did not differ in Vo, but Vo was lower than in control subjects (P < 0.001). There was no significant difference in Vo of type IIA fibers from symptomatic, asymptomatic, and control subjects. These results indicate that the MD mutation leads to a diminished force-generating capacity of the myofilaments in both symptomatic and asymptomatic individuals. The results further suggest that reduction in force-generating capacity at the cellular level develops prior to clinical weakness. © 2000 John Wiley & Sons, Inc. Muscle Nerve 23: 529–537, 2000.