We investigate the mechanisms behind muscle adaptations and maladaptations in disease. We are also investigating the fundamental causes of muscle fatigue.
The original focus of our research group is cellular mechanisms of skeletal muscle fatigue. We also study mechanisms behind muscle adaptations in response to training and maladaptations in disease, e.g. mitochondrial myopathies.
To a large extent our research relates to the complex interactions between force production, intracellular calcium handling, mitochondrial function and reactive oxygen/nitrogen species.
Our experiments are performed on adult muscle, including unique methods to study isolated fully intact muscle fibers. We find this essential because the functions we are studying differ markedly between adult muscle and immature muscle cells/muscle-like cell lines
Joseph Bruton Senior researcher Arthur Cheng Senior researcher Hans-Christer Holmberg Associated Niklas Ivarsson Research assistant Jan Lännergren Associated Malin Persson Postdoc Arturo Eduardo Uribe Gonzalez Graduate Student Håkan Westerblad Professor
Cellular mechanisms of skeletal muscle fatigue
Mechanisms behind skeletal muscle fatigue and recovery are studied mainly in single muscle fibres, but also in exercising human subjects. Mechanisms studied at present include the involvement of structural and functional changes in the intracellular Ca2+ release channels (the ryanodine receptors), reactive oxygen/nitrogen species (ROS), glycogen, and temperature effects.
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, mitochondrial myopathies. Our results show that the altered interactions between cellular Ca2+ handling, mitochondrial function and ROS metabolism are important in dysfunctional muscles.
We have an arsenal of techniques to study skeletal muscle function. These include unique methods to study single, fully intact fibers dissected from mouse, rat and human muscles.
We use standard fluorescence and confocal microscopy to measure ions and ROS in isolated muscle cells. Analytical biochemistry is used to measure muscle metabolites, enzyme activities and protein expression.
- Swedish Research Council
- Swedish National Centre for Research in Sports (in Swedish)
- Association Francaise contre les Myopathies
- Karolinska Institutet
Mechanisms of force depression caused by different types of physical exercise studied by direct electrical stimulation of human quadriceps muscle.
Eur. J. Appl. Physiol. 2016 Dec;116(11-12):2215-2224
Impaired Ca(2+) release contributes to muscle weakness in a rat model of critical illness myopathy.
Crit Care 2016 Aug;20(1):254
Dietary nitrate improves cardiac contractility via enhanced cellular Ca²⁺ signaling.
Basic Res. Cardiol. 2016 May;111(3):34
Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans.
Am. J. Physiol., Cell Physiol. 2016 May;310(10):C836-40
Reactive oxygen/nitrogen species and contractile function in skeletal muscle during fatigue and recovery.
J. Physiol. (Lond.) 2016 Sep;594(18):5149-60
Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise.
Proc. Natl. Acad. Sci. U.S.A. 2015 Dec;112(50):15492-7
Cyclophilin D, a target for counteracting skeletal muscle dysfunction in mitochondrial myopathy.
Hum. Mol. Genet. 2015 Dec;24(23):6580-7
Intracellular Ca(2+)-handling differs markedly between intact human muscle fibers and myotubes.
Skelet Muscle 2015 ;5():26
Muscle dysfunction associated with adjuvant-induced arthritis is prevented by antioxidant treatment.
Skelet Muscle 2015 ;5():20
Antioxidant treatments do not improve force recovery after fatiguing stimulation of mouse skeletal muscle fibres.
J. Physiol. (Lond.) 2015 Jan;593(2):457-72
α-Actinin-3: why gene loss is an evolutionary gain.
PLoS Genet. 2015 Jan;11(1):e1004908