Role of Ca2+/calmodulin-dependent kinases in skeletal muscle plasticity.
In skeletal muscle, the increase in intracellular Ca(2+) resulting from motor activation plays a key role in both contractile activity-dependent and fiber type-specific gene expression. These motor activation-dependent signals are linked to the amplitude and duration of the Ca(2+) transients that are decoded downstream by Ca(2+)-dependent transcriptional pathways. Evidence is mounting that the Ca(2+)/calmodulin-dependent kinases (CaMKs) such as CaMKII play an important role in regulating oxidative enzyme expression, mitochondrial biogenesis, and expression of fiber type-specific myofibrillar proteins. CaMKIV has been shown to promote mitochondrial biogenesis and a mild fast-to-slow fiber type transition but has recently been shown to not be required for activity-dependent changes in muscle phenotype. CaMKII is known to decode frequency-dependent information and is activated during hypertrophic growth and endurance adaptations and also is upregulated during muscle atrophy. CaMKII has also been shown to remain active in a Ca(2+)-independent manner after acute and prolonged exercise, and, therefore, is implicated as a mechanism for muscle memory. This mechanism can sense altered functional demands and trigger activation of an adaptational response that is dose dependently related to the activation level. This class of enzymes may therefore be the ideal decoders of information encoded by the intensity, frequency, and duty cycle of muscle activation and thus translate level of muscle activation into phenotypic adaptations through regulation of important muscle genes.
Chin
Eva R
ER
Research Pharmacology, Pfizer Global Research & Development, La Jolla Laboratories, 10724 Science Center Drive, San Diego, CA 92121, USA. eva.r.chin@pfizer.com
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000502:physiology*; D005082:Physical Exertion / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D009124:Muscle Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium