Parvalbumin deficiency in fast‐twitch muscles leads to increased ‘slow‐twitch type’ mitochondria, but does not affect the expression of fiber specific proteins

Parvalbumin (PV), a small cytosolic protein belonging to the family of EF‐hand calcium‐binding proteins, is highly expressed in mammalian fast‐twitch muscle fibers. By acting as a ‘slow‐onset’ Ca 2+ buffer, PV does not affect the rapid contraction phase, but significantly contributes to increase the rate of relaxation, as demonstrated in PV–/– mice. Unexpectedly, PV–/– fast‐twitch muscles were considerably more resistant to fatigue than the wild‐type fast‐twitch muscles. This effect was attributed mainly to the increased fractional volume of mitochondria in PV–/– fast‐twitch muscle, extensor digitorum longus , similar to levels observed in the slow‐twitch muscle, soleus . Quantitative analysis of selected mitochondrial proteins, mitochondrial DNA‐encoded cytochrome oxidase c subunit I and nuclear DNA‐encoded cytochrome oxidase c subunit Vb and F1‐ATPase subunit β revealed the PV–/– tibialis anterior mitochondria composition to be almost identical to that in wild‐type soleus , but not in wild‐type fast‐twitch muscles. Northern and western blot analyses of the same proteins in different muscle types and in liver are indicative of a complex regulation, probably also at the post‐transcriptional level. Besides the function in energy metabolism, mitochondria in both fast‐ and slow‐twitch muscles act as temporary Ca 2+ stores and are thus involved in the shaping of Ca 2+ transients in these cells. Previously observed altered spatio‐temporal aspects of Ca 2+ transients in PV–/– muscles are sufficient to up‐regulate mitochondria biogenesis through the probable involvement of both calcineurin‐ and Ca 2+ /calmodulin‐dependent kinase II‐dependent pathways. We propose that ‘slow‐twitch type’ mitochondria in PV–/– fast muscles are aimed to functionally replace the slow‐onset buffer PV based on similar kinetic properties of Ca 2+ removal.