Deficiency in parvalbumin increases fatigue resistance in fast-twitch muscle and upregulates mitochondria

The soluble Ca2+-binding protein parvalbumin (PV) is expressed at high leve ls in fast-twitch muscles of mice. Deficiency of PV in knockout mice (PV -/ -) slows down the speed of twitch relaxation, while maximum force generated during tetanic contraction is unaltered. We observed that PV-deficient fas t-twitch muscles were significantly more resistant to fatigue than were the wild type. Thus components involved in Ca2+ homeostasis during the contrac tion-relaxation cycle were analyzed. No upregulation of another cytosolic C a2+-binding protein was found. Mitochondria are thought to play a physiolog ical role during muscle relaxation and were thus analyzed. The fractional v olume of mitochondria in the fast-twitch muscle extensor digitorum longus ( EDL) was almost doubled in PV -/- mice, and this was reflected in an increa se of cytochrome c oxidase. A faster removal of intracellular Ca2+ concentr ation ([Ca2+](i)) 200-700 ms after fast-twitch muscle stimulation observed in PV -/- muscles supports the role for mitochondria in late [Ca2+](i) remo val. The present results also show a significant increase of the density of capillaries in EDL muscles of PV -/- mice. Thus alterations in the dynamic s of Ca2+ transients detected in fast-twitch muscles of PV -/- mice might b e linked to the increase in mitochondria volume and capillary density, whic h contribute to the greater fatigue resistance of these muscles.