The role of in vivo Ca2+ signals acting on Ca2+-calmodulin-dependent proteins for skeletal muscle plasticity

Skeletal muscle fibres are highly heterogeneous regarding size, metabolism and contractile function. They also show a large capacity for adaptations in response to alterations in the activation pattern. A major part of this activity-dependent plasticity relies on transcriptional alterations controlled by intracellular Ca2+ signals. In this review we discuss how intracellular Ca2+ fluctuations induced by activation patterns likely to occur in vivo control muscle properties via effects on Ca2+-calmodulin-dependent proteins. We focus on two such Ca2+ decoders: calcineurin and Ca2+-calmodulin-dependent protein kinase II. Inherent Ca2+ transients during contractions differ rather little between slow-and fast-twitch muscle fibres and this difference is unlikely to have any significant impact on the activity of Ca2+ decoders. The major exception to this is fatigue-induced changes in Ca2+ transients that occur in fast-twitch fibres exposed to high-intensity activation typical of slow-twitch motor units. In conclusion, the cascade from neural stimulation pattern to Ca2+-dependent transcription is likely to be central in maintaining the fibre phenotypes in both fast-and slow-twitch fibres. Moreover, changes in Ca2+ signalling (e. g. induced by endurance training) can result in altered muscle properties (e.g. increased mitochondrial biogenesis) and this plasticity involves other signalling pathways.