We investigate the mechanisms behind muscle adaptations and maladaptations in disease. We are also investigating the fundamental causes of muscle fatigue.
Our original research focus was to discover the cellular causes of fatigue in skeletal muscle. The accumulated findings of our group and other groups have firmly established that muscle fatigue is not caused by increased lactate or acidosis. Our studies of the basic mechanisms underlying muscle fatigue continue.
Numerous common disorders, such as diabetes and general inflammatory diseases, are associated with skeletal and cardiac muscle dysfunction. Therefore, a large proportion of our research is dedicated to uncovering the mechanisms that produce functional adaptations and maladaptations in skeletal and cardiac muscle. Diseases studied in this context include type 2-diabetes, rheumatoid arthritis, and mitochondrial myopathies.
Cellular mechanisms of skeletal muscle fatigue
Mechanisms behind skeletal muscle fatigue are studied mainly in single muscle fibres. Mechanisms studied at present include the involvement of reactive oxygen species, ROS, temperature effects, and phosphorylation of key proteins.
Mechanisms underlying the impaired muscle function associated with common diseases
Numerous common diseases are associated with muscle weakness and early fatigue development. This can be due to muscle wasting, but also to intrinsic problems in the muscle cells leading to decreased force production. We are studying mechanisms behind muscle dysfunctions in mouse models of for example rheumatoid arthritis and mitochondrial myopathies. Our results show that the altered interactions between cellular calcium handling, mitochondrial function and ROS (reactive oxygen species) metabolism are important in dysfunctional muscles.
Mechanisms of glucose uptake in skeletal muscle
Glucose uptake increases in muscles exposed to insulin or after exercise. We study the role of calcium in insulin-mediated glucose uptake.
Another research interest is the role of ketone bodies in the induction of insulin resistance. Contraction-stimulated glucose uptake is known to occur via pathways different to those used by insulin. Exercise increases mitochondrial respiration and ROS (reactive oxygen species) production. We are investigating the role of reactive oxygen species in exercise-mediated glucose transport.
Cellular mechanisms of cardiac dysfunction
Impaired intracellular calcium handling appears to be a general problem in many diseases such as diabetes. We measure shortening calcium in isolated cardiomyocytes. We also measure reactive oxygen/nitrogen species (ROS) and our results show a complex interplay between calcium, ROS and contractile function. Experiments are performed on wildtype animals and mouse disease models, for example type 2-diabetes, rheumatoid arthritis and mitochondrial myopathies.
We have an arsenal of techniques with which to study mammalian skeletal and cardiac muscle function. These include the use of whole muscles, muscle bundles and single dissected muscle fibres. In some experiments, we use enzymatically dissociated cardiac myocytes and skeletal muscle fibres either fresh or after culturing for several days.
We use laser confocal microscopy and fluorescent probes to measure ions and proteins in isolated cardiac and skeletal muscle cells. A wide range of electrophysiological techniques including patch clamp are used. Analytical biochemistry is used to measure a wide range of muscle metabolites, enzyme activities and protein expression.
- Swedish Research Council
- Swedish National Centre for Research in Sports (in Swedish)
- Swedish Heart and Lung Foundation
- Association Francaise contre les Myopathies
- Karolinska Institutet
- National Institutes of Health (NIH)
Improved exercise performance and increased aerobic capacity after endurance training of patients with stable polymyositis and dermatomyositis.
Arthritis Res. Ther. 2013 ;15(4):R83
Residual force depression following muscle shortening is exaggerated by prior eccentric drop jump exercise.
J. Appl. Physiol. 2013 Oct;115(8):1191-5
Effects of N-acetylcysteine on isolated mouse skeletal muscle: contractile properties, temperature dependence, and metabolism.
Pflugers Arch. 2014 Mar;466(3):577-85
Doublet discharge stimulation increases sarcoplasmic reticulum Ca2+ release and improves performance during fatiguing contractions in mouse muscle fibres.
J. Physiol. (Lond.) 2013 Aug;591(Pt 15):3739-48
Muscle glycogen stores and fatigue.
J. Physiol. (Lond.) 2013 Sep;591(Pt 18):4405-13
Impaired mitochondrial respiration and decreased fatigue resistance followed by severe muscle weakness in skeletal muscle of mitochondrial DNA mutator mice.
J. Physiol. (Lond.) 2012 Dec;590(Pt 23):6187-97
TLR4 as receptor for HMGB1 induced muscle dysfunction in myositis.
Ann. Rheum. Dis. 2013 Aug;72(8):1390-9
Non-crossbridge calcium-dependent stiffness in slow and fast skeletal fibres from mouse muscle.
J. Muscle Res. Cell. Motil. 2012 Mar;32(6):403-9