Non-contractile Ca2+ Signalling in Skeletal Muscle

As well as stimulating muscle contraction, Ca²⁺ also has many other roles in skeletal muscle.

Mitochondria

As mentioned here, several steps in the TCA cycle can be influenced by Ca²⁺ signalling. To be more specific, the activity of several enzymes, including ATP synthase itself, are enhanced by Ca²⁺. This works out pretty well: more Ca²⁺ release causes more contractile activity and therefore an increase in ATP consumption, but at the same time Ca²⁺ also increases ATP production. This phenomenon is known as "Excitation-Metabolism Coupling," and is facilitated by the close proximity of mitochondria to the SR.

Muscle phenotype

Muscle fibre type is not fixed: it can change between slow and fast. One transcription factor important in determining muscle fibre phenotype is NFAT. NFAT can be activated by calcineurin, which is activated by Ca²⁺-calmodulin (yup, the same Ca²⁺-calmodulin responsible for activating MLCK). Slow fibres, with a more constant Ca²⁺ release as compared to fast fibres, activate NFAT to a greater extent than fast fibres. When NFAT is activated, it maintains the production of slow contractile proteins and the slow fibre phenotype. When NFAT is no longer activated, slow contractile proteins are decreased, causing a change in phenotype to the fast phenotype.

Growth and repair

There are several other signalling pathways that can be activated by Ca²⁺. These include MAPKs (MAP kinases) such as ERK, JNK and p38, which play a role in cellular growth and repair. These MAPKs can also be activated by stretching and movement. Stretching and movement can further activate MAPKs (and other Ca²⁺ signalling pathways) by opening mechanosensitive Ca²⁺ channels and letting in more Ca²⁺.

Non-shivering thermogenesis (NST)

Non-shivering thermogenesis is heat production not caused by shivering (hence the name). In mammals, NST is usually associated with brown fat, which is a tissue specialised for heat production. Skeletal muscle, however, may also be able to do NST. Since cold acclimatisation causes an increase in ryanodine receptors and SERCA (and therefore an increase in Ca²⁺ release and uptake), it is thought that the movement of Ca²⁺ in and out of the SR, and the increased ATP usage by the SR pumps, causes the increase in heat generation during NST.

Store-mediated Ca²⁺ entry

This works pretty much the same way as in smooth muscle. See here if you can't remember.