LAUSR

One of the most important cytosolic Ca2+ buffers present in mouse fast-twitch myofibers, but not in human myofibers, is parvalbumin (PV). Previous work using conventional PV knockout mice suggests that lifelong PV ablation increases fatigue resistance, possibly due to compensations in mitochondrial volume. In this work, PV gene ablation was induced only in adult mice (PV-KO), and contractile and cytosolic Ca2+ responses during fatigue were studied in isolated muscle and intact single myofibers. Results were compared to control littermates (PV-Ctr). We hypothesized that the reduced myofiber cytosolic Ca2+ buffering developed only in adult PV-KO mice leads to a larger cytosolic free Ca2+ concentration ([Ca2+]c) during repetitive contractions, increasing myofiber fatigue resistance. Extensor digitorum longus (EDL) muscles from PV-KO mice had higher force in unfused stimulations (~50%, P<0.05) and slowed relaxation (~46% higher relaxation time, P<0.05) vs PV-Ctr, but muscle fatigue resistance or fatigue-induced changes in relaxation were not different between genotypes (P>0.05). In intact single myofibers from flexor digitorum brevis (FDB) muscles, basal and tetanic [Ca2+]c during fatiguing contractions were higher in PV-KO (P<0.05), accompanied by a greater slowing in estimated sarcoplasmic reticulum (SR) Ca2+ pumping vs PV-Ctr myofibers (~84% reduction, P<0.05), but myofiber fatigue resistance was not different between genotypes (P>0.05). Our results demonstrate that although the estimated SR Ca2+ uptake was accelerated in PV-KO, the total energy demand by the major energy consumers in myofibers, the cross-bridges and SR Ca2+ ATPase, were not altered enough to affect the energy supply for contractions, and therefore fatigue resistance remained unaffected.