The Role of Thin Filament Calcium Sensitivity in Modulating Relaxation Time of Soleus and EDL Skeletal Muscle

Abstract

The mechanical process of skeletal muscle relaxation; myofilament detachment, calcium sequestration, and Ca2+-Troponin dissociation, has been well understood for some time. However, many questions about the physiological and pathophysiological role of relaxation time (RT) remain. The objective of this study is to determine if relaxation time is a dynamic property that can be modulated by altering the calcium sensitivity of the thin filament.Our data suggests that the relaxation time of Het mice (utrn+/-,MDX, a moderate Duchenne Muscular Dystrophy (DMD) phenotype) is significantly increased in soleus muscle (predominantly slow-twitch) across a broad frequency range and also at some higher frequencies in EDL muscle (predominantly fast-twitch) compared to WT, age matched mice. We hypothesize that relaxation is a dynamic and controllable process and delayed relaxation is an effect of DMD disease progression.The present research plan was designed to study the effects of altered relaxation time on wildtype and Het mouse soleus and EDL contractile properties using an adeno-associated virus to express engineered troponin C with increased or decreased calcium sensitivities. Contractile properties are assessed by twitch force, tetanic force, time to peak, half relaxation time, and comparing force-frequency response curves. While the basic mechanical process of skeletal muscle relaxation is known, our data demonstrates a need for further investigation into the physiological control of this process and the role that thin filament calcium sensitivity (Troponin C) plays in the regulation of relaxation.