Diffusional anisotropy is induced by subcellular barriers in skeletal muscle.
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.
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01 Jul 2009TL;DR: A detailed discussion of magnetic field gradient methods applied to Magnetic Resonance Imaging (MRI) is included, alongside extensive referencing throughout, providing a timely, definitive book to the subject, ideal for researchers in the fields of physics, chemistry and biology.
Abstract: Translational motion in solution, either diffusion or fluid flow, is at the heart of chemical and biochemical reactivity. Nuclear Magnetic Resonance (NMR) provides a powerful non-invasive technique for studying the phenomena using magnetic field gradient methods. Describing the physical basis of measurement techniques, with particular emphasis on diffusion, balancing theory with experimental observations and assuming little mathematical knowledge, this is a strong, yet accessible, introduction to the field. A detailed discussion of magnetic field gradient methods applied to Magnetic Resonance Imaging (MRI) is included, alongside extensive referencing throughout, providing a timely, definitive book to the subject, ideal for researchers in the fields of physics, chemistry and biology.
371 citations
TL;DR: DW‐MRS has been used to estimate the dimensions of the cellular elements that restrict intracellular metabolite diffusion in muscle and nerve tissue and can provide novel information on the cellular response to pathophysiological changes in relation to a range of disorders.
Abstract: MR offers unique tools for measuring molecular diffusion. This review focuses on the use of diffusion-weighted MR spectroscopy (DW-MRS) to non-invasively quantitate the translational displacement of endogenous metabolites in intact mammalian tissues. Most of the metabolites that are observed by in vivo MRS are predominantly located in the intracellular compartment. DW-MRS is of fundamental interest because it enables one to probe the in situ status of the intracellular space from the diffusion characteristics of the metabolites, while at the same time providing information on the intrinsic diffusion properties of the metabolites themselves. Alternative techniques require the introduction of exogenous probe molecules, which involves invasive procedures, and are also unable to measure molecular diffusion in and throughout intact tissues. The length scale of the process(es) probed by MR is in the micrometer range which is of the same order as the dimensions of many intracellular entities. DW-MRS has been used to estimate the dimensions of the cellular elements that restrict intracellular metabolite diffusion in muscle and nerve tissue. In addition, it has been shown that DW-MRS can provide novel information on the cellular response to pathophysiological changes in relation to a range of disorders, including ischemia and excitotoxicity of the brain and cancer.
189 citations
TL;DR: The ideas of compartmentation came into existence from the necessity to explain important physiological phenomena, in particular in heart research and in cardiac electrophysiology, which demonstrated the physiological importance of the biophysical and biochemical mechanisms described in this review.
Abstract: The history of the development of the ideas and research of organized metabolic systems during last three decades is shortly reviewed. The cell cytoplasm is crowded with solutes, soluble macromolecules such as enzymes, nucleic acids, structural proteins and membranes. The high protein density within the large compartments of the cells predominantly determines the major characteristics of cellular environment such as viscosity, diffusion and inhomogeneity. The fact that the solvent viscosity of cytoplasm is not substantially different from the water is explained by intracellular structural heterogeneity: the intrinsic macromolecular density is relatively low within the interstitial voids in the cell because many soluble enzymes are apparently integral parts of the insoluble cytomatrix and are not distributed homogeneously. The molecular crowding and sieving restrict the mobility of very large solutes, binding severely restrict the mobility of smaller solutes. One of consequence of molecular crowding and hindered diffusion is the need to compartmentalize metabolic pathway to overcome diffusive barriers. Although the movement of small molecules is slowed down in the cytoplasm, the metabolism can successfully proceed and even be facilitated by metabolite channeling which directly transfers the intermediate from one enzyme to an adjacent enzyme without the need of free aqueous-phase diffusion. The enhanced probability for intermediates to be transferred from one active site to the other by sequential enzymes requires stable or transient interactions of the relevant enzymes, which associate physically in non-dissociable, static multienzyme complexes--metabolones, particles containing enzymes of a part or whole metabolic systems. Therefore, within the living cell the metabolism depends on the structural organization of enzymes forming microcompartments. Since cells contain many compartments and microenvironments, the measurement of the concentration of metabolites in whole cells or tissues gives an average cellular concentration and not that which is actually sensed by the active site of a specific enzyme. Thus, the microcompartmentation could provide a mechanism which can control metabolic pathways. Independently and in parallel to the developments described above, the ideas of compartmentation came into existence from the necessity to explain important physiological phenomena, in particular in heart research and in cardiac electrophysiology. These phenomena demonstrated the physiological importance of the biophysical and biochemical mechanisms described in this review.
172 citations
Cites background from "Diffusional anisotropy is induced b..."
...Indeed, recent more detailed analysis, by using the same pulsed-gradient (31)P-NMR showed that the diffusion of ATP and PCr is anisotropic in muscle cells [54, 55]....
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TL;DR: The ability of DTI to differentiate between functionally different muscles in the same region of the body on the basis of their diffusive properties was demonstrated, and the relationship between diffusive and architectural properties was determined.
Abstract: The aim of this study was to examine the diffusive properties of adjacent muscles at rest, and to determine the relationship between diffusive and architectural properties, which are task-specific to muscles. The principle, second, and third eigenvalues, trace of the diffusion tensor, and two anisotropic parameters, ellipsoid eccentricity (e) and fractional anisotropy (FA), of various muscles in the human calf were calculated by diffusion tensor imaging (DTI). Linear correlations of the calculated parameters to the muscle physiological cross-sectional area (PCSA), which is proportional to maximum muscle force, were performed to ascertain any linear relation between muscle architecture and diffusivity. Images of the left calf were acquired from six healthy male volunteers. Seven muscles were investigated in this study. These comprised the soleus, lateral gastrocnemius, medial gastrocnemius, posterior tibialis, anterior tibialis, extensor digitorum longus, and peroneus longus. All data were presented as the mean and standard error of the mean (SEM). In general, differences in diffusive parameter values occurred primarily between functionally different muscles. A strong correlation was also found between PCSA and the third eigenvalue, e, and FA. A mathematical derivation revealed a linear relationship between PCSA and the third eigenvalue as a result of their dependence on the average radius of all fibers within a single muscle. These findings demonstrated the ability of DTI to differentiate between functionally different muscles in the same region of the body on the basis of their diffusive properties.
164 citations
Additional excerpts
...Previously published results have shown that the measured diffusion coefficient in multi-compartmental systems, such as biological tissue, vary functionally at short and long mixing times (Mitra et al. 1992; Latour et al. 1994; Gibbs 1997; Kinsey et al. 1999)....
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TL;DR: Analysis of cellular nucleotide fluxes and nucleotide-dependent gating of the ATP-sensitive K+ (KATP) channel revealed a diffusional barrier within the submembrane space, preventing direct reception of cytosolic signals.
144 citations
References
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1,940 citations
TL;DR: In this article, a study of bipolar pulse pairs in PFGNMR (pulsed field gradient NMR) is presented, which shows a drastic reduction in eddy currents for short (≃ 1 millisecond), closely spaced (<1 ms) gradient pulses.
1,319 citations
TL;DR: The diffusion behavior of intracranial water in the cat brain and spine was examined with the use of diffusion-weighted magnetic resonance (MR) imaging, in which the direction of the diffusion-sensitizing gradient was varied between the x, y, and z axes of the magnet.
Abstract: The diffusion behavior of intracranial water in the cat brain and spine was examined with the use of diffusion-weighted magnetic resonance (MR) imaging, in which the direction of the diffusion-sensitizing gradient was varied between the x, y, and z axes of the magnet. At very high diffusion-sensitizing gradient strengths, no clear evidence of anisotropic water diffusion was found in either cortical or subcortical (basal ganglia) gray matter. Signal intensities clearly dependent on orientation were observed in the cortical and deep white matter of the brain and in the white matter of the spinal cord. Greater signal attenuation (faster diffusion) was observed when the relative orientation of white matter tracts to the diffusion-sensitizing gradient was parallel as compared to that obtained with a perpendicular alignment. These effects were seen on both premortem and immediate postmortem images obtained in all axial, sagittal, and coronal views. Potential applications of this MR imaging technique included the stereospecific evaluation of white matter in the brain and spinal cord and in the characterization of demyelinating and dysmyelinating diseases.
1,164 citations
TL;DR: It was proposed in 1951 that contracting muscle fibers liberate creatine, which acts to produce an acceptor effect--later called respiratory control--on the muscle mitochondria, which established a molecular basis for a phosphorylcreatine-creatine shuttle for energy transport in heart and skeletal muscle.
Abstract: In order to explain the insulin-like effect of exercise, it was proposed in 1951 that contracting muscle fibers liberate creatine, which acts to produce an acceptor effect--later called respiratory control--on the muscle mitochondria. The development of this notion paralleled the controversy between biochemists and physiologists over the delivery of energy for muscle contraction. With the demonstration of functional compartmentation of creatine kinase on the mitochondrion, it became clear that the actual form of energy transport in the muscle fiber is phosphorylcreatine. The finding of an isoenzyme of creatine phosphokinase attached to the M-line region of the myofibril revealed the peripheral receptor for the mitochondrially generated phosphorylcreatine. This established a molecular basis for a phosphorylcreatine-creatine shuttle for energy transport in heart and skeletal muscle and provided an explanation for the inability to demonstrate experimentally a direct relation between muscle activity and the concentrations of adenosine triphosphate and adenosine diphosphate.
739 citations
TL;DR: In this article, three new stimulated echo sequences involving applied field gradient pulses, of amplitude ga, together with RF pulses, are described, and the echo attenuation and systematic error caused by g0 and g0ga terms, respectively, are greatly reduced.
673 citations