Purine nucleotide cycle as a possible anaplerotic process in rat skeletal muscle

Summary The intermediates of the purine nucleotide cycle (PNC) stimulated pyruvate oxidation by isolated skeletal muscle mitochondria in a system containing mitochondria and cytosol from rat skeletal muscle. Thus, in skeletal muscle the PNC might be involved in the anaplerotic supply of tricarboxylic acid cycle intermediates.Acknowledgment. This work was supported by a grant from the Polish Academy of Science within the project MR II.1.2.4.     

AMP-activated protein kinase in skeletal muscle: From structure and localization to its role as a master regulator of cellular metabolism

The AMP-activated protein kinase (AMPK) is a metabolite sensing serine/threonine kinase that has been termed the master regulator of cellular energy metabolism due to its numerous roles in the regulation of glucose, lipid, and protein metabolism. In this review, we first summarize the current literature on a number of important aspects of AMPK in skeletal muscle. These include the following: (1) the structural components of the three AMPK subunits (i.e. AMPKα, β, and γ), and their differential localization in response to stimulation in muscle; (2) the biochemical regulation of AMPK by AMP, protein phosphatases, and its three known upstream kinases, LKB1, Ca²⁺/calmodulin-dependent protein kinase kinase (CaMKK), and transforming growth factor-β-activated kinase 1 (TAK1); (3) the pharmacological agents that are currently available for the activation and inhibition of AMPK; (4) the physiological stimuli that activate AMPK in muscle; and (5) the metabolic processes that AMPK regulates in skeletal muscle. Received 04 May 2008; received after revision 14 June 2008; accepted 14 July 2008     

Insulin action in cultured human skeletal muscle cells during differentiation: assessment of cell surface GLUT4 and GLUT1 content

In mature human skeletal muscle, insulin-stimulated glucose transport is mediated primarily via the GLUT4 glucose transporter. However, in contrast to mature skeletal muscle, cultured muscle expresses significant levels of the GLUT1 glucose transporter. To assess the relative contribution of these two glucose transporters, we used a novel photolabelling techniques to assess the cell surface abundance of GLUT1 and GLUT4 specifically in primary cultures of human skeletal muscle. We demonstrate that insulin-stimulated glucose transport in cultured human skeletal muscle is mediated by GLUT4, as no effect on GLUT1 appearance at the plasma membrane was noted. Furthermore, GLUT4 mRNA and protein increased twofold (p < 0.05), after differentiation, whereas GLUT1 mRNA and protein decreased 55% (p < 0.005). Incubation of differentiated human skeletal muscle cells with a non-peptide insulin mimetic significantly (p < 0.05) increased glucose uptake and glycogen synthesis. Thus, cultured myotubes are a useful tool to facilitate biological and molecular validation of novel pharmacological agents aimed to improve glucose metabolism in skeletal muscle.     

Voltage-clamp analysis of the sodium and potassium currents in skeletal muscle fibres treated with 4-aminopyridine

Summary External application of low concentrations of 4-aminopyridine blocks potassium currents without affecting sodium currents in pieces of single frog skeletal muscle fibres. The blockade of potassium currents was voltage-dependent, being partially relieved on depolarization.This study was supported by a grant from the Oficina técnica de Desarrollo Cientifico of the University of Chile (Project 4437-R, 1977).     

The variation in active tension with sarcomere length in vertebrate skeletal muscle and its relation to fibre width

Zusammenfassung Die Relation zwischen tetanischer Spannung und Sarkomerabstand wurde an der isolierten Semitendinosus-Faser des Frosches bei verschiedenen Graden von Hydratisierung der Faser untersucht. Es trat keine Veränderung des Länge-Spannungs-Verhältnisses auf, obwohl die Relation zwischen Länge-und Querschnittsdimensionen der Muskelfaser durch Immersion in den verschiedenen osmotischen Medien beträchtlich verschoben werden konnte. Die Ergebnisse stützen die Annahme, dass das Länge-Spannungs-Diagramm durch den Grad des Überlappens zwischen den A- und I-Filamenten und nicht durch den Querabstand zwischen den Filamenten bestimmt wird.

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This study was supported by grants from the Muscular Dystrophy Association of America and from the Swedish Medical Research Council (No. B67-14x-184-03).     

Distribution of inulin-carboxy-C14 in heart and skeletal muscle with respect to in vivo and in vitro extracellular space determinations

Zusammenfassung Gleichmässige Indikatorverteilung im Gewebe ist Ausdruck für Konzentrationsausgleich zwischen Blutstrom bzw. Inkubationsmedium und Extrazellulärraum. Es wurde ein zentraler Block aus einem Gewebsstück herausgeschnitten und die Konzentration von Inulin-carboxyl-C¹⁴ darin mit der im peripheren oberflächlichen Gewebe verglichen. Im Myokard des linken Ventrikels und im Soleusmuskel fand sich in vivo eine gleichmässige Verteilung, in vitro hingegen nicht; selbst bei einer Inkubationsdauer von 5 h in einem als optimal anzusehenden Milieu. Damit ist die Methode, wahre Extrazellulärräume in vitro zu messen, fragwürdig. Hingegen hat sich die Echtheit von in-vivo-Bestimmungen bestätigt.

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This investigation was supported in part by U.S. Public Health Service Research Grant No. HE-09791 from the National Heart Institute and General Research Support Grant No. SO1-FR-05525 from the Division of Research Facilities and Resources, and in part by a grant from the John A. Hartford Foundation.     

The effects of chronic alcohol ingestion in mice on contractile properties of cardiac and skeletal muscle: a comparison with normal and dehydrated-malnourished controls.

In vitro isometric contractile tension was measured in heart and skeletal muscle in 3 groups of mice: 1. a control group, 2. a group maintained for 27 weeks on 20% alcohol, and 3. a group whose fluid intake was restricted to the extent equaling that which occurred in the alcohol treated animals. Results showed a reduction in cardiac twitch tension in both the alcohol and fluid restricted group, as compared to normal controls. We therefore consider that dehydration per se may play an important role in the etiology of alcoholic cardiomyopathy.     

Atypical muscle cells in the wall of the renal calix and pelvis with a note on their possible significance

Zusammenfassung Es werden atypische Muskelzellen beschrieben, welche sich um die Nierenbeckenkelche und die Nierenbecken befinden. Dabei handelt es sich um glatte Muskelfasern, die wahrscheinlich im Nierenbecken-Uretergebiet endigen und deren Einfluss auf die Aktivität des Ureters diskutiert wird.

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I wish to thank Prof. G. A. G.Mitchell for his interest and Mr. A. N.Waas for valuable technical assistance.