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Junctophilins (JP1 & JP2) are expressed in skeletal muscle and are the primary proteins involved in transverse (T)-tubule and sarcoplasmic reticulum (SR) membrane apposition. During the performance of eccentric contractions, the apposition of T-tubule and SR membranes may be disrupted, resulting in excitation-contraction (EC) coupling failure and thus reduced force-producing capacity. In this study, we made three primary observations: 1) Through the first three days after the performance of 50 eccentric contractions in vivo by the left hindlimb anterior crural muscles of female mice, both JP1 and JP2 were significantly reduced by ~50 and 35%, respectively, while no reductions were observed after the performance of non-fatiguing concentric contractions; 2) following the performance of a repeated bout 50 eccentric contractions in vivo, only JP1 was immediately reduced (~30%) but recovered by 3d post-injury in tandem with the recovery of strength and EC coupling; and 3) following the performance of 10 eccentric contractions at either 15 or 35˚C by isolated mouse EDL muscle, isometric force, EC coupling, and JP1 and JP2 were only reduced after the 35˚C eccentric contractions. Regression analysis of JP1 and JP2 content in TA and EDL muscles from each set of experiments indicated that JP damage is significantly associated with early (0 – 3d) strength deficits after performing eccentric contractions (R = 0.49; P < 0.001). As a whole, the results of this study indicate that JP damage plays in role in early force deficits due to EC coupling failure following the performance of eccentric contractions.

Aberrant phenotypes of airway smooth muscle cells are central to the pathophysiology of asthma. The hypercontractile nature of these cells and hypertrophy are the key reasons for the excessive narrowing of the airways observed in allergic asthma. Although previous studies have indicated a role of enhanced content of smMLCK in modulating the contractile reactivity, as well as an indication of hypertrophy of HASM cells in asthmatic conditions, the effect of IgE on the expression of smMLCK in HASM cells is not fully understood. In this study, we demonstrate that IgE augments the expression of smMLCK at the mRNA and protein level. Inhibition of IgE binding with anti-FcεRI blocking antibody, Syk silencing, pharmacological inhibitors to MAPK (ERK1/2, p38, and JNK) and PI3K significantly diminished the IgE-mediated smMLCK expression in HASM cells. Finally, we found that IgE, similar to metacholine induces the contraction of HASM cells grown on collagen gel matrix. Our data suggest that IgE stimulates the phosphorylation of ERK, P38, STAT3 and induces the dephosphorylation of smMLCK to phosphorylate myosin regulatory light chain in HASM cells. Taken together, our data suggest a modulatory role of IgE in regulating the contractile machinery and hypertrophic phenotype of HASM cells.

Differentiation of skeletal muscle fibers into fast and slow twitch appears to be under control of the stimulation pattern imparted by motoneurons innervating these muscle fibers. Fast twitch muscle fibers receive intense stimulation for brief periods of time while slow twitch muscle fibers receive less intense stimulation for much longer periods of time. This study examined thickness of Zlines in dually innervated skeletal muscle fibers of slow twitch soleus muscle following transplantation of the fast extensor digitorum longus (EDL) nerve onto the surface of the soleus. Eight individual dually innervated fibers were dissected from four transplanted mouse soleus muscles and examined with a transmission electron microscope. Z-lines in these dually innervated fibers were thinner (mean = 83 nm) than control soleus (mean = 123 nm) and thicker than control EDL (mean = 57 nm). A significant difference (p< .002) was also found between Z-line thickness near the foreign EDL endplate (mean = 81 nm) versus the original soleus endplate (mean = 85 nm). These results suggest the factors controlling protein synthesis in skeletal muscle fibers have both a global and localized effect. / Department of Physiology and Health Science

Aberrant phenotypes of airway smooth muscle cells are central to the pathophysiology of asthma. The hypercontractile nature of these cells and hypertrophy are the key reasons for the excessive narrowing of the airways observed in allergic asthma. Although previous studies have indicated a role of enhanced content of smMLCK in modulating the contractile reactivity, as well as an indication of hypertrophy of HASM cells in asthmatic conditions, the effect of IgE on the expression of smMLCK in HASM cells is not fully understood. In this study, we demonstrate that IgE augments the expression of smMLCK at the mRNA and protein level. Inhibition of IgE binding with anti-FcεRI blocking antibody, Syk silencing, pharmacological inhibitors to MAPK (ERK1/2, p38, and JNK) and PI3K significantly diminished the IgE-mediated smMLCK expression in HASM cells. Finally, we found that IgE, similar to metacholine induces the contraction of HASM cells grown on collagen gel matrix. Our data suggest that IgE stimulates the phosphorylation of ERK, P38, STAT3 and induces the dephosphorylation of smMLCK to phosphorylate myosin regulatory light chain in HASM cells. Taken together, our data suggest a modulatory role of IgE in regulating the contractile machinery and hypertrophic phenotype of HASM cells.

Thesis (Ph. D.)--University of Hawaii at Manoa, 1995. / Includes bibliographical references (leaves 60-67). / Microfiche. / xii, 67 leaves, bound ill. 29 cm

Thesis (MAppSc in Physiotherapy)--University of South Australia, 1995

Thesis (M.Sc.)--York University, 2006. Graduate Programme in Kinesiology and Health Science. / Typescript. Includes bibliographical references (leaves 75-80). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR19737

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 7 uppsatser.

Thesis (Ph.D.)--University of Wollongong, 2006. / Typescript. Includes bibliographical references: leaf 271-302.