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Timothy S. Moerland

Other affiliations: University of Washington
Bio: Timothy S. Moerland is an academic researcher from Florida State University. The author has contributed to research in topics: Skeletal muscle & Myosin. The author has an hindex of 15, co-authored 24 publications receiving 905 citations. Previous affiliations of Timothy S. Moerland include University of Washington.

Papers
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Journal ArticleDOI
TL;DR: The proposition that muscle cell types have different contents of phosphocreatine (PCr), ATP, and Pi is tested by 31P NMR spectroscopy and HPLC analyses of adult rat and mouse muscles containing various volume fractions of different fiber types, establishing an additional criterion upon which to distinguish skeletal muscle cells, one based on the resting content of bioenergetically important metabolites.
Abstract: We tested the proposition that muscle cell types have different contents of phosphocreatine (PCr), ATP, and Pi by 31P NMR spectroscopy and HPLC analyses of adult rat and mouse muscles containing various volume fractions of different fiber types. There was a 2-fold difference in the PCr content between muscles with a high volume fraction of fiber types 1 and 2x versus those with fast-twitch (types 2a and 2b) fiber types. Pi content was low, and PCr and ATP contents were high in muscles with large contents of type 2b and 2a fibers; the reverse was true in muscles with a large volume fraction of type 1 and 2x fibers. There is a large range in the Pi/PCr ratios in normal resting muscles, from less than 0.05 in type 2 to 0.51 in type 1 fibers, depending upon the distribution of their component fiber types. In all muscles, the peak area resulting from the beta phosphate of ATP constituted approximately 13% of the sum of all peak areas observable in the 31P spectrum. Fiber types 2a and 2b were not distinguishable, and the content of type 2x fibers was similar to type 1 fibers. From the profile of these metabolites, we could distinguish only two classes of fibers. For type 2a and 2b fibers, the intracellular concentrations were 8 mM ATP, 39 mM total creatine, 32 mM PCr, 0.8 mM Pi, and 8 microM ADP. For type 1 and 2x fibers, these quantities were 5 mM ATP, 23 mM total creatine, 16 mM PCr, 6 mM Pi, and 11 microM ADP. Thus our results establish an additional criterion upon which to distinguish skeletal muscle cells, one based on the resting content of bioenergetically important metabolites. These results also provide the basis for estimating skeletal muscle fiber-type composition from noninvasive NMR spectroscopic data.

283 citations

Journal ArticleDOI
TL;DR: This work is the first example of diffusional anisotropy induced by readily identifiable intracellular structures, and the sarcoplasmic reticulum and mitochondria appear to be the principal intrACEllular structures that inhibit mobility in an orientation‐dependent manner.
Abstract: The time- and orientational-dependence of phosphocreatine (PCr) diffusion was measured using pulsed-field gradient nuclear magnetic resonance (PFG-NMR) as a means of non-invasively probing the intracellular diffusive barriers of skeletal muscle. Red and white skeletal muscle from fish was used because fish muscle cells are very large, which facilitates the examination of diffusional barriers in the intracellular environment, and because they have regions of very homogeneous fiber type. Fish were cold-acclimated (5 degrees C) to amplify the contrast between red and white fibers. Apparent diffusion coefficients, D, were measured axially, D(axially) and radially, D(radially), in small muscle strips over a time course ranging from 12 to 700 ms. Radial diffusion was strongly time dependent in both fiber types, and D decreased with time until a steady-state value was reached at a diffusion time approximately 100 ms. Diffusion was also highly anisotropic, with D(axially) being higher than D(radially) for all time points. The time scale over which changes in D(radially) occurred indicated that the observed anisotropy was not a result of interactions with the thick and thin filament lattice of actin and myosin or restriction within the cylindrical sarcolemma, as has been previously suggested. Rather, the sarcoplasmic reticulum (SR) and mitochondria appear to be the principal intracellular structures that inhibit mobility in an orientation-dependent manner. This work is the first example of diffusional anisotropy induced by readily identifiable intracellular structures.

94 citations

Journal ArticleDOI
TL;DR: The effects of changes in electrical charge on the temperature sensitivity of DATP were measured under various conditions of temperature, pH, and pMg2+.

93 citations

Journal ArticleDOI
TL;DR: Measurements of the intracellular diffusion coefficients of ATP and creatine phosphate in stable, isolated preparations of skeletal muscle were made by means of pulsed field gradient (PFG) 31P NMR by using a PFG NMR probe specifically designed for small, superfused biological samples.
Abstract: Measurements of the intracellular diffusion coefficients (Di) of ATP and creatine phosphate (PCr) in stable, isolated preparations of skeletal muscle were made by means of pulsed field gradient (PFG) 31P NMR Experiments used a PFG NMR probe specifically designed for small, superfused biological samples This provided a magnetic field gradient in the z axis of up to 195 G/cm with minimal eddy currents DiATP and DiPCr in white (fast, glycolytic) skeletal muscle from goldfish (Carassius auratus) were determined to be 248 +/- 033 and 349 +/- 033 x 10(-6) cm2/s, respectively, at 25 degrees C and a diffusion time of approximately 19 ms For comparison with Di values, diffusion coefficients of ATP and PCr also were measured in solutions of ionic composition similar to that of fish muscle cytosol The in vitro diffusion coefficients of ATP and PCr were 354 +/- 011 and 528 +/- 008 x 10(-6) cm2/s, respectively, at 25 degrees C

70 citations

Journal ArticleDOI
TL;DR: The model shows that the proximal stimulus for temperature-induced changes in mitochondrial volume density in muscle is not a disruption in intracellular diffusion of high-energy phosphates, and gradients were attenuated in cold-acclimated animals by cold-induced increases in mitochondrial density.
Abstract: Thermal acclimation results in dramatic changes in the fractional volume of mitochondria within skeletal muscle of teleost fish. We investigated the hypothesis that changes in mitochondrial volume represent a compensatory response to temperature-induced changes in intracellular diffusion coefficients (D) of the high-energy phosphate compounds ATP and creatine phosphate (PCr). Using 31P nuclear magnetic resonance spectroscopy, we determined DPCr and DATP in goldfish (Carassius auratus) skeletal muscle at 25 degrees C and 5 degrees C: DPCr was 3.28 +/- 0.18 x 10(-6) cm2s-1 at 25 degrees C and 2.00 +/- 0.90 x 10(-6) cm2s-1 at 5 degrees C: DATP was 2.13 +/- 0.16 x 10(-6) cm2s-1 at 25 degrees C and was estimated to be 1.30 x 10(-6) cm2s-1 at 5 degrees C. There was no evidence for an effect of acclimation temperature or fiber type on DATP or DPCr. A mathematical reaction-diffusion model was used to calculate profiles of [ATP], [PCr] and the free energy of ATP hydrolysis (delta GATP) in activated goldfish muscle fibers at 5 degrees C and 25 degrees C. The results showed spatial and temporal constancy of [ATP], [PCr] and delta GATP in red fibers at both temperatures, regardless of changes in acclimation temperature or mitochondrial density. The model also showed spatial and temporal constancy of [ATP] in white fibers at 5 degrees C and 25 degrees C, but gradients in [PCr] and delta GATP developed in white fibers under all conditions of temperature and acclimation temperature. These gradients were attenuated in cold-acclimated animals by cold-induced increases in mitochondrial density. However, the model shows that the proximal stimulus for temperature-induced changes in mitochondrial volume density in muscle is not a disruption in intracellular diffusion of high-energy phosphates.

52 citations


Cited by
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Journal ArticleDOI
TL;DR: A comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism is presented, encompassing the pathways and regulation of Cr biosynthesis and degradation, species and tissue distribution of the enzymes and metabolites involved, and of the inherent implications for physiology and human pathology.
Abstract: The goal of this review is to present a comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism, encompassing the pathways and regulation of Cr biosynthesis an...

2,332 citations

Journal ArticleDOI
TL;DR: Mammalian skeletal muscle comprises different fiber types, whose identity is first established during embryonic development by intrinsic myogenic control mechanisms and is later modulated by neural and hormonal factors.
Abstract: Mammalian skeletal muscle comprises different fiber types, whose identity is first established during embryonic development by intrinsic myogenic control mechanisms and is later modulated by neural and hormonal factors. The relative proportion of the different fiber types varies strikingly between species, and in humans shows significant variability between individuals. Myosin heavy chain isoforms, whose complete inventory and expression pattern are now available, provide a useful marker for fiber types, both for the four major forms present in trunk and limb muscles and the minor forms present in head and neck muscles. However, muscle fiber diversity involves all functional muscle cell compartments, including membrane excitation, excitation-contraction coupling, contractile machinery, cytoskeleton scaffold, and energy supply systems. Variations within each compartment are limited by the need of matching fiber type properties between different compartments. Nerve activity is a major control mechanism of the fiber type profile, and multiple signaling pathways are implicated in activity-dependent changes of muscle fibers. The characterization of these pathways is raising increasing interest in clinical medicine, given the potentially beneficial effects of muscle fiber type switching in the prevention and treatment of metabolic diseases.

2,107 citations

Journal ArticleDOI
TL;DR: Research into the mechanisms that regulate mitochondrial transport is an important emerging frontier into the pathogenesis of several major neurological disorders.
Abstract: Mitochondria have a number of essential roles in neuronal function. Their complex mobility patterns within neurons are characterized by frequent changes in direction. Mobile mitochondria can become stationary or pause in regions that have a high metabolic demand and can move again rapidly in response to physiological changes. Defects in mitochondrial transport are implicated in the pathogenesis of several major neurological disorders. Research into the mechanisms that regulate mitochondrial transport is thus an important emerging frontier.

716 citations

Journal ArticleDOI
TL;DR: Skeletal myoblasts can establish new muscle tissue when grafted into injured hearts, and this muscle can contract when stimulated electrically, because the grafts convert to fatigue-resistant, slow twitch fibers, this new muscle may be suited to a cardiac work load.
Abstract: Myocardial infarcts heal by scarring because myocardium cannot regenerate. To determine if skeletal myoblasts could establish new contractile tissue, hearts of adult inbred rats were injured by freeze-thaw, and 3-4.5 x 10(6) neonatal skeletal muscle cells were transplanted immediately thereafter. At 1 d the graft cells were proliferating and did not express myosin heavy chain (MHC). By 3 d, multinucleated myotubes were present which expressed both embryonic and fast fiber MHCs. At 2 wk, electron microscopy demonstrated possible satellite stem cells. By 7 wk the grafts began expressing beta-MHC, a hallmark of the slow fiber phenotype; coexpression of embryonic, fast, and beta-MHC continued through 3 mo. Transplanting myoblasts 1 wk after injury yielded comparable results, except that grafts expressed beta-MHC sooner (by 2 wk). Grafts never expressed cardiac-specific MHC-alpha. Wounds containing 2-wk-old myoblast grafts contracted when stimulated ex vivo, and high frequency stimulation induced tetanus. Furthermore, the grafts could perform a cardiac-like duty cycle, alternating tetanus and relaxation, for at least 6 min. Thus, skeletal myoblasts can establish new muscle tissue when grafted into injured hearts, and this muscle can contract when stimulated electrically. Because the grafts convert to fatigue-resistant, slow twitch fibers, this new muscle may be suited to a cardiac work load.

690 citations

Book ChapterDOI
TL;DR: A simple transition scheme has emerged from the multitude of data collected on fiber type conversions under a variety of conditions, and it is now clear that fiber type transitions do not proceed in immediate jumps from one extreme to the other, but occur in a graded and orderly sequential manner.
Abstract: Mammalian skeletal muscle is an extremely heterogeneous tissue, composed of a large variety of fiber types. These fibers, however, are not fixed units but represent highly versatile entities capable of responding to altered functional demands and a variety of signals by changing their phenotypic profiles. This adaptive responsiveness is the basis of fiber type transitions. The fiber population of a given muscle is in a dynamic state, constantly adjusting to the current conditions. The full range of adaptive ability spans fast to slow characteristics. However, it is now clear that fiber type transitions do not proceed in immediate jumps from one extreme to the other, but occur in a graded and orderly sequential manner. At the molecular level, the best examples of these stepwise transitions are myofibrillar protein isoform exchanges. For the myosin heavy chain, this entails a sequence going from the fastest (MHCIIb) to the slowest (MHCI) isoform, and vice-versa. Depending on the basal protein isoform profile and hence the position within the fast-slow spectrum, the adaptive ranges of different fibers vary. A simple transition scheme has emerged from the multitude of data collected on fiber type conversions under a variety of conditions.

651 citations