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Item A Molecular Mechanism for Autoinhibition of Myosin Light Chain Kinases(Elsevier, 1993) Gallagher, Patricia J.; Herring, B. Paul; Trafny, Andrzej; Sowadski, Janusz; Stull, James T.; Anatomy, Cell Biology and Physiology, School of MedicineIt is postulated that basic residues within the inhibitory region of myosin light chain kinase (MLCK) bind acidic residues within the catalytic core to maintain the kinase in an inactive form. In this study, we identified residues within the catalytic cores of the skeletal and smooth muscle MLCKs that may bind basic residues in inhibitory region. Acidic residues within the catalytic core of the rabbit skeletal and smooth muscle MLCKs were mutated and the kinetic properties of the mutant kinases determined. Mutation of 6 and 8 acidic residues in the skeletal and smooth muscle MLCKs, respectively, result in mutant MLCKs with decreases in KCaM (the concentration of calmodulin required for half-maximal activation of myosin light chain kinase) value ranging from 2- to 100-fold. Two inhibitory domain binding residues identified in each kinase also bind a basic residue in light chain substrate. The remaining mutants all have wild-type Km values for light chain. The predicted inhibitory domain binding residues are distributed in a linear fashion across the surface of the lower lobe of the proposed molecular model of the smooth muscle MLCK catalytic core. As 6 of the inhibitory domain binding residues in the smooth muscle MLCK are conserved in other Ca2+/calmodulin-dependent protein kinases, the structural basis for autoinhibition and activation may be similar.Item Accurate and representative decoding of the neural drive to muscles in humans with multi-channel intramuscular thin-film electrodes(Wiley, 2015-09-01) Muceli, Silvia; Poppendieck, Wigand; Negro, Francesco; Yoshida, Ken; Hoffmann, Klaus P.; Butler, Jane E.; Gandevia, Simon C.; Farina, Dario; Department of Biomedical Engineering, School of Engineering and TechnologyIntramuscular electrodes developed over the past 80 years can record the concurrent activity of only a few motor units active during a muscle contraction. We designed, produced and tested a novel multi-channel intramuscular wire electrode that allows in vivo concurrent recordings of a substantially greater number of motor units than with conventional methods. The electrode has been extensively tested in deep and superficial human muscles. The performed tests indicate the applicability of the proposed technology in a variety of conditions. The electrode represents an important novel technology that opens new avenues in the study of the neural control of muscles in humans. We describe the design, fabrication and testing of a novel multi-channel thin-film electrode for detection of the output of motoneurones in vivo and in humans, through muscle signals. The structure includes a linear array of 16 detection sites that can sample intramuscular electromyographic activity from the entire muscle cross-section. The structure was tested in two superficial muscles (the abductor digiti minimi (ADM) and the tibialis anterior (TA)) and a deep muscle (the genioglossus (GG)) during contractions at various forces. Moreover, surface electromyogram (EMG) signals were concurrently detected from the TA muscle with a grid of 64 electrodes. Surface and intramuscular signals were decomposed into the constituent motor unit (MU) action potential trains. With the intramuscular electrode, up to 31 MUs were identified from the ADM muscle during an isometric contraction at 15% of the maximal force (MVC) and 50 MUs were identified for a 30% MVC contraction of TA. The new electrode detects different sources from a surface EMG system, as only one MU spike train was found to be common in the decomposition of the intramuscular and surface signals acquired from the TA. The system also allowed access to the GG muscle, which cannot be analysed with surface EMG, with successful identification of MU activity. With respect to classic detection systems, the presented thin-film structure enables recording from large populations of active MUs of deep and superficial muscles and thus can provide a faithful representation of the neural drive sent to a muscle.Item The arteries of the human sternocleidomastoid muscle(1969) Blair, Keith D.Item Cyclic nucleotide phosphodiesterases from rat liver and skeletal muscle(1973) Ingebretsen, Carmel GrandeItem Evaluation of the sources and disposition of the citric acid cycle intermediates in skeletal muscle(1977) Lee, Sung-Hee ChoItem Regulation of glycolysis in rat skeletal muscle extracts(1977) Wu, Tsai-feng Lin