Deficiency in parvalbumin increases fatigue resistance in fast-twitch muscle and upregulates mitochondria.
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.
Chen
G
G
Institute of Anatomy, University of Bern, CH-3012 Bern, Switzerland.
Carroll
S
S
Racay
P
P
Dick
J
J
Pette
D
D
Traub
I
I
Vrbova
G
G
Eggli
P
P
Celio
M
M
Schwaller
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D018763:Muscle Fatigue / Q000502:physiology*; D018656:Muscle Fibers, Fast-Twitch / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D010320:Parvalbumins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding
D010320:Parvalbumins; D002118:Calcium