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Deficiency in parvalbumin increases fatigue resistance in fast-twitch muscle and upregulates mitochondria
Abstract:
The soluble Ca2+-binding protein parvalbumin (PV) is expressed at high levels 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 fast-twitch muscles were significantly more resistant to fatigue than were the wild type. Thus components involved in Ca2+ homeostasis during the contraction-relaxation cycle were analyzed. No upregulation of another cytosolic Ca2+-binding protein was found. Mitochondria are thought to play a physiological role during muscle relaxation and were thus analyzed. The fractional volume of mitochondria in the fast-twitch muscle extensor digitorum longus (EDL) was almost doubled in PV -/- mice, and this was reflected in an increase of cytochrome c oxidase. A faster removal of intracellular Ca2+ concentration ([Ca2+]i) 200-700 ms after fast-twitch muscle stimulation observed in PV -/- muscles supports the role for mitochondria in late [Ca2+]i removal. The present results also show a significant increase of the density of capillaries in EDL muscles of PV -/- mice. Thus alterations in the dynamics of Ca2+ transients detected in fast-twitch muscles of PV -/- mice might be linked to the increase in mitochondria volume and capillary density, which contribute to the greater fatigue resistance of these muscles.
Insights
Mice lacking parvalbumin (PV) show slower muscle relaxation but enhanced fatigue resistance. This increased endurance is linked to more mitochondria and capillaries in their fast-twitch muscles.
Area of Science:
- Muscle physiology
- Cellular biology
- Calcium homeostasis
Background:
- Parvalbumin (PV) is a soluble Ca2+-binding protein abundant in fast-twitch muscles.
- PV deficiency in knockout mice (PV -/-) slows twitch relaxation but does not affect maximum tetanic force.
- PV -/- mice exhibit significantly greater fatigue resistance in fast-twitch muscles compared to wild-type.
Purpose of the Study:
- To investigate the mechanisms behind the enhanced fatigue resistance in PV-deficient fast-twitch muscles.
- To analyze components involved in Ca2+ homeostasis during the muscle contraction-relaxation cycle.
- To explore the role of mitochondria and capillary density in muscle fatigue.
Main Methods:
- Analysis of Ca2+-binding proteins and mitochondrial content in PV -/- and wild-type mouse muscles.
- Measurement of fractional mitochondrial volume and cytochrome c oxidase activity.
- Assessment of intracellular Ca2+ concentration ([Ca2+]i) dynamics post-stimulation.
- Evaluation of capillary density in fast-twitch extensor digitorum longus (EDL) muscles.
Main Results:
- PV deficiency did not lead to upregulation of other cytosolic Ca2+-binding proteins.
- Fractional mitochondrial volume in EDL muscles of PV -/- mice was nearly doubled, with increased cytochrome c oxidase.
- Faster removal of intracellular Ca2+ ([Ca2+]i) was observed in PV -/- muscles 200-700 ms after stimulation.
- A significant increase in capillary density was found in EDL muscles of PV -/- mice.
Conclusions:
- Mitochondria play a role in the late removal of intracellular Ca2+ during muscle relaxation.
- Increased mitochondria volume and capillary density in PV-deficient muscles contribute to their enhanced fatigue resistance.
- Alterations in Ca2+ transient dynamics are linked to improved muscle endurance in the absence of parvalbumin.