Troponin C mutations alter twitch kinetics and force-frequency relationship of fast and slow twitch skeletal muscle

Abstract

Troponin C (TnC) is critically involved in the contraction of striated muscle. The role of TnC on the mechanical process of skeletal muscle has been thoroughly investigated. However, the impact of TnC mutations on the force-frequency relationship (FFR) of skeletal muscle is yet to be investigated. The objective of this study is to determine the effect of TnC mutations on the force-frequency relationship and contractile kinetics in fast and slow-twitch skeletal muscle. To investigate this key question, we measured the extensor digitorum longus (EDL) and soleus force-frequency response in a murine model with a TnC mutation (expressed after TnCL48QAAV or TnCD73NAAV injection) that causes increased calcium sensitivity (L48Q) or a decreased calcium sensitivity (D73N) and compared the FFR to the wildtype counterparts.