Show simple item record

dc.contributor.authorGittings, William J.
dc.date.accessioned2015-12-21T20:06:47Z
dc.date.available2015-12-21T20:06:47Z
dc.identifier.urihttp://hdl.handle.net/10464/7769
dc.description.abstractThis thesis investigated the modulation of dynamic contractile function and energetics of work by posttetanic potentiation (PTP). Mechanical experiments were conducted in vitro using software-controlled protocols to stimulate/determine contractile function during ramp shortening, and muscles were frozen during parallel incubations for biochemical analysis. The central feature of this research was the comparison of fast hindlimb muscles from wildtype and skeletal myosin light chain kinase knockout (skMLCK-/-) mice that does not express the primary mechanism for PTP: myosin regulatory light chain (RLC) phosphorylation. In contrast to smooth/cardiac muscles where RLC phosphorylation is indispensable, its precise physiological role in skeletal muscle is unclear. It was initially determined that tetanic potentiation was shortening speed dependent, and this sensitivity of the PTP mechanism to muscle shortening extended the stimulation frequency domain over which PTP was manifest. Thus, the physiological utility of RLC phosphorylation to augment contractile function in vivo may be more extensive than previously considered. Subsequent experiments studied the contraction-type dependence for PTP and demonstrated that the enhancement of contractile function was dependent on force level. Surprisingly, in the absence of RLC phosphorylation, skMLCK-/- muscles exhibited significant concentric PTP; consequently, up to ~50% of the dynamic PTP response in wildtype muscle may be attributed to an alternate mechanism. When the interaction of PTP and the catchlike property (CLP) was examined, we determined that unlike the acute augmentation of peak force by the CLP, RLC phosphorylation produced a longer-lasting enhancement of force and work in the potentiated state. Nevertheless, despite the apparent interference between these mechanisms, both offer physiological utility and may be complementary in achieving optimal contractile function in vivo. Finally, when the energetic implications of PTP were explored, we determined that during a brief period of repetitive concentric activation, total work performed was ~60% greater in wildtype vs. skMLCK-/- muscles but there was no genotype difference in High-Energy Phosphate Consumption or Economy (i.e. HEPC: work). In summary, this thesis provides novel insight into the modulatory effects of PTP and RLC phosphorylation, and through the observation of alternative mechanisms for PTP we further develop our understanding of the history-dependence of fast skeletal muscle function.en_US
dc.language.isoengen_US
dc.publisherBrock Universityen_US
dc.subjectpotentiationen_US
dc.subjectmyosin phosphorylationen_US
dc.subjectskeletal muscle physiologyen_US
dc.titleForce potentiation as a modulator of contractile performance: Implications for control of skeletal muscle force and energetics of worken_US
dc.typeElectronic Thesis or Dissertationen_US
dc.degree.namePh.D. Applied Health Sciencesen_US
dc.degree.levelDoctoralen_US
dc.contributor.departmentApplied Health Sciences Programen_US
dc.degree.disciplineFaculty of Applied Health Sciencesen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record