Low frequency mechanical vibrations (<100 Hz) are naturally generated by skeletal muscles during voluntary contractions. Recording of these vibrations at the muscle surface are called surface mechanomyograms (S-MMGs). In this study, S-MMGs were recorded over a 3 x 5 grid of skin mounted accelerometers on the biceps brachii muscle during submaximal voluntary isometric contractions with the arm in a pronated position for ten healthy and young male subjects with no overt sign of neuromuscular diseases. For a given pair of accelerometers, the spatial coherence of S-MMG is a measure of the similarity of the S-MMG signals propagating between those two sensors. Two common techniques to estimate the spatial coherence for narrowband S-MMG signals, namely the magnitude squared coherence function and the maximum of the time-domain cross-correlation function, were found to yield similar results. In particular, high spatial coherence values were measured for sensor pairs aligned along the proximal to distal ends of the biceps, i.e. the longitudinal direction. On the other hand, the spatial coherence values for sensor pairs oriented perpendicular to the muscle fiber, i.e. along the transverse direction, were found to be significantly lower. This finding indicates that coherent S-MMGs were mainly propagating along the muscle fibers direction (longitudinal) of the biceps brachii within a frequency band varying between 10Hz to 50Hz. Additionally, the spatial coherence of S-MMGs along the longitudinal direction was found to decrease with increasing frequency and increasing sensor separation distance and to increase with contraction level varying between 20% to 60% of the maximum contraction level.

Thesis (M.S.)--West Virginia University, 2001. / Title from document title page. Document formatted into pages; contains vii, 65 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 59-62).

Thesis (Ph. D.)--York University, 1999. Graduate Programme in Biology. / Typescript. Includes bibliographical references. Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pNQ56221.

Thesis (M. Sc.)--York University, 2001. Graduate Programme in Kinesiology and Health Science. / Typescript. Includes bibliographical references. Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pMQ71585.

published_or_final_version / Physiology / Master / Master of Medical Sciences

Contracting skeletal muscle releases ATP into the interstitial space where it is subsequently broken down to adenosine by the action of ecto-5’-nucleotidase. Both ATP and adenosine are vasodilators that contribute to the exercise hyperaemia. However, the mechanism for the release of ATP from muscle during exercise remains unknown. Cystic fibrosis transmembrane conductance regulator (CFTR) is involved in ATP release from muscle at low intracellular pH: this study was performed to investigate whether CFTR was involved in the ATP release from skeletal muscle during contractions. Experiments were performed in rats anaesthetised with sodium pentobarbitone and breathing spontaneously. A microdialysis probe was placed in one gastrocnemius muscle: ATP was determined in interstitial microdialysate samples using a bioluminescence assay. The sciatic nerve was stimulated to induce two bouts of muscle contractions, separated by a recovery period of 40 mins; one of the inhibitors was administered prior to the second bout of contractions. Muscle contractions elevated the interstitial ATP by 1500 to 3000%. In the control experiments, no drug was given: both the contractile force and the increase in interstitial ATP were reproducible in repeated contraction bouts. Infusion of a specific inhibitor of CFTR, CFTRinh-172, did not alter the contractile force, but significantly lowered the interstitial ATP during muscle contractions, suggesting that CFTR was involved in the contraction-induced ATP release. Similarly, infusion of the Protein Kinase A inhibitor, KT5720, significantly reduced interstitial ATP during muscle contractions without altering contractile force, suggesting that CFTR in skeletal muscle is activated through the cAMP/PKA pathway. The increase in interstitial ATP during muscle contraction was also inhibited by the Na/H exchanger inhibitor, amiloride, or the Na/Ca exchanger inhibitor, SN6. It has been also shown that two gap junction hemichannel inhibitors, gadolinium and carbenoxolone, could attenuate the increase of ATP during muscle contraction. These data suggest that CFTR, activated through the cAMP/protein kinase A pathway, is involved in the ATP release during muscle contraction, and that activation of the Na/H exchanger and Na/Ca exchanger was also required, indicating that the signal transduction mechanism for CFTR activation during muscle contractions may be similar to that which is reported to occur at low pH. The preliminary data showed that the gap junction hemichannels might mediate the ATP release from skeletal muscle cells during muscle contraction. / published_or_final_version / Physiology / Master / Master of Philosophy

In living systems, ion channels are membrane transport proteins that provide pathways for the passive diffusion of ions through lipid membranes. The flow of ions across membranes is the basis of many important physiological processes, including but not limited to the regulation of membrane potential, transepithelial transport and cell volume. While many efforts have been made to understand the biological roles of natural ion channels, the biological activities of artificial ion channels remain largely unknown. Recently, it was reported that a small molecule 1, which forms synthetic chloride (Cl–) channels in membranes via self-assembly, is capable of modulating vascular functions. In this thesis, novel small molecules that are structurally similar to 1 are shown to form artificial ion channels in membranes. Together with 1, the effects of these small molecules on the contractile activities of smooth muscles and epithelial ion transport are explored. The therapeutic implications of the findings are also discussed. A collection of small molecules was screened using liposome-based fluorescence assays. In these assays, the ability of the synthetic compounds to modulate membrane potential was monitored. The screening yielded compound 3 that formed synthetic potassium (K+) channels in liposomal membranes, although the liposome-based fluorescence experiments suggested that 3 also transported Cl–. Two derivatives of 3, namely, compounds 2 and 4 were also examined. Single-channel recording experiments suggested that 2 forms synthetic Cl– channels in liposomal membranes. The effects of compounds 2 and 3 on the functions of the vascular smooth muscle are explored. Using confocal imaging, it was shown that both 2 and 3 counteracted the effects of high-K+ depolarizing solution on membrane potential and intracellular Ca2+ concentration ([Ca2+]i) in cultured vascular smooth muscle cells. 2 and 3 also relaxed mice aortic rings pre-contracted with high-K+ solution. These observations can be explained in terms of the Cl– transporting functions of 2 and 3. To determine the potential for developing the compounds into bronchodilators, the effects of compounds 1 and 3 on the contractile activities of the airway smooth muscle (ASM) were explored using organ bath technique. The contractile activities of the trachea isolated from Sprague-Dawley (SD) rats were first characterized. Among the contractile agents used, only potassium chloride (KCl), cholinergic agonists, serotonin and endothelin-1 were contractile to the SD rat trachea. 1 and 3 relaxed the ASM pre-contracted with KCl, whereas the contractions induced by other agonists were not affected. The ability of compounds 2, 3 and 4 to modulate ion transport across cultured epithelia was tested by the short-circuit current measurement technique. It was shown that the compounds were capable of inducing Cl– secretion when applied to the apical side of airway and colonic epithelia. Importantly, the synthetic compounds induced apical Cl– secretion in immortalized cystic fibrosis (CF) bronchial epithelia. This suggests that the synthetic compounds may be used to correct the anion transport defect in CF epithelia. In summary, the small-molecule based synthetic ion channels demonstrated two important general functions of natural ion channels, namely, the regulation of membrane potential and epithelial ion transport. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

No description available.

No description available.

The purpose of this investigation was to examine the contractile properties of individual slow and fast myofibers in response to various training periods throughout a collegiate cross-country season in male runners. Muscle biopsies were obtained from the gastrocnemius of five runners at three time points during the season; after a summer aerobic training phase (T1); after an 8 week period of intense training (T2) and after a 4 week taper period (T3). Absolute (4.6±0.3 L/min) and relative (71±0.7 mI/kg/min) maximal oxygen consumption were unchanged during the study duration. Run performance (8 km) improved 3% from T1 to T2 (27:26 to 26:38 min:sec) and 1% from T2 to T3 (26:21 min:sec). A total of 328 individual myofibers were isolated and studied at 15°C. MHC I diameter was 3% lower (P < 0.05) at T2 compared to T1 and 4% smaller at T3 compared to T2. MHC I and Ila fibers were 18 and 11 % stronger (P < 0.05) respectively, from T1 to T2. MHC I fibers produced 9% less force (P < 0.05) after the taper (T2-T3) while MHC Ila fibers were 9% stronger (P < 0.05). Specific tension (Po/CSA) increased (P < 0.05) 38 and 26% for MHC I and Ila fibers, respectively from T1 to T2 and was unchanged with the taper. Maximal shortening velocity (Vo) of the MHC I fibers decreased (P < 0.05) 23% from T1 to T2 and 17% from T2 to T3. MHC I peak power decreased (P < 0.05) 20% from T1 to T2 and 25% from T2 to T3. Power corrected for cell size decreased (P < 0.05) 15% from T2 to T3 and was 24% lower at T3 compared to T1 for the MHC I fibers only. MHC Ila diameter, Vo, peak and normalized power were unaltered during the study duration. These data suggest that myocellular function is sensitive to changes in run training and it appears that MHC I fibers are moreaffected than MHC IIa fibers. Furthermore, the increase in interval training with the taper may have offset the modest reduction in training volume and prevented any positive adaptations at the cellular level. / Human Performance Laboratory