Browsing by Author "Powers, Krysta"

Now showing 1 - 2 of 2
  • Thumbnail Image
    ItemOpen Access
    A Proposed Mechanism for Enhanced Titin-Based Force during Ca2+-activation
    (2017) Powers, Krysta; Herzog, Walter; Pollack, Gerald; Schmidt, Tannin; Syme, Douglas; Nishikawa, Kiisa; Shemanko, Carrie; Federico, Salvatore
    When an active skeletal muscle sarcomere is stretched, it generates more force after the stretch is completed when compared to a contraction at the same corresponding length. This mechanical property of skeletal muscle defies explanation by any conventional mechanism of contraction. Surmounting evidence indicates that the explanation for enhanced force following active stretch may be provided by the titin protein in the sarcomere, which becomes stiffer during Ca2+-activation. This thesis explores the mechanisms by which titin force is enhanced in actively stretched sarcomeres. Known to stiffen in the presence of Ca2+, the first study quantifies the contribution of Ca2+ to enhanced titin force, showing that an alternative mechanism accounts for the majority of titin force enhancement. The mechanism is further investigated using chemical inhibition of cross-bridges which shows that titin force enhancement is initiated with the development of contractile force. The next set of studies increase support for an interdependence of titin force enhancement and contractile force, showing that titin force enhancement is essentially eliminated and contractile force is decreased in sarcomeres with muscular dystrophy with myositis (mdm), a genetic mutation affecting the titin protein. The final study seeks to determine whether mechanical deficiencies in titin force enhancement are observed in a less reduced, single fiber preparation. Mutant fibers generated comparable contractile force and total force following active stretch beyond filament overlap as control fibers. Titin force enhancement was abolished in some mutant fibers and measured in other mutant fibers suggesting that the mdm mutation differentially affects fibers (and titin) in skeletal muscle. Passive force was increased in mutant fibers, showing that alternative structural components in a fiber can re-establish enhanced active stiffness in the absence of titin force enhancement. Collectively, the findings from this thesis show that titin-based force enhancement is an inherent property of skeletal muscle. The mechanism of titin force enhancement is crucial to sarcomere mechanics; as in its absence, sarcomeres generate less force and alternative structures to titin establish a comparable increase in active stiffness.
  • Thumbnail Image
    ItemOpen Access
    A new paradigm for muscle contraction
    (Frontiers in Physiology, 2015-06-10) Herzog, Walter; Powers, Krysta; Johnston, Kaleena; Duvall, Mike
    Muscle contraction has fascinated lay people and scientists for centuries. However, a good understanding of how muscle contraction occurs seemed only possible once microscopy techniques had evolved to a level where basic structural features, such as the regular cross striation patterns of fibers, could be observed in the late 19th century. In the early 20th century, a stimulated muscle was simply considered a new elastic body (Gasser and Hill,1924). Shortening and work production took place with a fixed amount of energy tha twas stored in this body and evolved elastically through stimulation. However, this notion was proven false when Wallace Fenn demonstrated that muscle produced an increasing amount of total energy when increasing its mechanical work output; an observation that was in contradiction with Hill’s elastic body theory (Fenn, 1923,1924). Specifically, Fenn, who worked in the laboratory of Hill and measured heat and work production in frog muscles, found that a muscle allowed to shorten liberated more energy than a muscle held isometrically or a muscle that was stretched. This has become known as the Fenn effect in muscle physiology.