The Effect of Muscle Length on Post-Tetanic Potentiation of skMLCK-/- and C57BL/6 Mouse EDL Muscles

Abstract

Post-tetanic potentiation of force in fast skeletal muscle is inversely related to muscle or sarcomere length, diminishing at longer lengths. This relationship has been mainly attributed to the structural effects of the primary mechanism of potentiation, phosphorylation of the regulatory light chain (RLC) of myosin, which is catalyzed by skeletal myosin light chain kinase (skMLCK). The purpose of this thesis was to compare the relationship between isometric twitch force potentiation and muscle or sarcomere length in fast twitch extensor digitorum longus (EDL) muscles from wildtype and skMLCK-/- mice. It was hypothesized that in addition to reduced potentiation, skMLCK-/- muscles without the ability to phosphorylate the RLC would also display an altered length-dependence of potentiation compared to wildtype muscles with RLC phosphorylation. The main finding was that although twitch potentiation was greater in WT muscles at all lengths, the relationship between potentiation and muscle length was similar in both WT and skMLCK-/- muscles. This indicates that the length-dependence of potentiation cannot necessarily be attributed to RLC phosphorylation. Thus, additional mechanisms, possibly related to Ca2+ handling, thick filament mechanosensing and length-dependent activation may participate in the length-dependence of potentiation displayed by murine fast muscle models.