Year: 2014
Type: article
Abstract: content in muscle fibers (Figure 2).How does this process occur?Research done during the last 10 years has begun to answer this question at the molecular level (Figure 3).Much of this work has relied on the study of genetically modified mice (eg, that depicted in Figure 4).Rodents are natural-born endurance exercisers.Provided with in-cage running wheels, most mice will voluntarily run 5 to 8 km per night.Although this level of exercise does not precisely model the human condition, the ability to model endurance exercise in an organism amenable to genetic manipulation has proven invaluable.Conceptually, the adaptation process can be divided into mechanisms that sense endurance activity and mechanisms that carry out the desired adaptations (Figure 3). How Does Muscle Sense Exercise Activity? Nerves and EnergyKey molecular sensors of exercise include the calcium oscillations and other signaling cascades activated by neural stimulation and the profoundly altered metabolic state of contracting myofibers.Stimulation of muscle by motor nerves generates cytosolic calcium transients that are detected by various intracellular pathways, including those regulated by the calcium/calmodulin-modulated phosphatase (calcineurin) and kinase (CaMK).Continuous low-amplitude transients, typical of endurance activity, activate calcineurin.Transgenic overexpression of calcineurin in skeletal muscle of mice promotes the formation of slow red fibers. 19Conversely, genetic deletion of calcineurin or treatment with calcineurin inhibitors has the opposing effect, blocking exercise-induced adaptations. 32CaMK is likely another decoder of calcium transients. 33CaMKII is the predominant isoform in skeletal muscle, but experiments with transgenic expression of a constitutively active CaMKIV isoform showed that CaMK can promote the formation of slow red fibers. 30Conversely, mice with decreased CAMKII activity have lower expression of slow genes. 34Sensing of calcium
Source: Circulation
Authors: Glenn C. Rowe, Adeel Safdar, Zolt Arany
Language: English
Subfield: Complementary and alternative medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2149255972