%0 Journal Article
%T Mitochondria can substitute for parvalbumin to lower cytosolic calcium levels in the murine fast skeletal muscle.
%A Marcucci L
%A Nogara L
%A Canato M
%A Germinario E
%A Raffaello A
%A Carraro M
%A Bernardi P
%A Pietrangelo L
%A Boncompagni S
%A Protasi F
%A Paolocci N
%A Reggiani C
%J Acta Physiol (Oxf)
%V 240
%N 9
%D 2024 Sep 30
%M 39077881
%F 7.523
%R 10.1111/apha.14208
%X <B>OBJECTIVE: </B>Parvalbumin (PV) is a primary calcium buffer in mouse fast skeletal muscle fibers. Previous work showed that PV ablation has a limited impact on cytosolic Ca2+ ([Ca2+]cyto) transients and contractile response, while it enhances mitochondrial density and mitochondrial matrix-free calcium concentration ([Ca2+]mito). Here, we aimed to quantitatively test the hypothesis that mitochondria act to compensate for PV deficiency.<BR><B>METHODS: </B>We determined the free Ca2+ redistribution during a 2 s 60 Hz tetanic stimulation in the sarcoplasmic reticulum, cytosol, and mitochondria. Via a reaction-diffusion Ca2+ model, we quantitatively evaluated mitochondrial uptake and storage capacity requirements to compensate for PV lack and analyzed possible extracellular export.<BR><B>RESULTS: </B>[Ca2+]mito during tetanic stimulation is greater in knock-out (KO) (1362 ± 392 nM) than in wild-type (WT) (855 ± 392 nM), p < 0.05. Under the assumption of a non-linear intramitochondrial buffering, the model predicts an accumulation of 725 μmoles/L fiber (buffering ratio 1:11 000) in KO, much higher than in WT (137 μmoles/L fiber, ratio 1:4500). The required transport rate via mitochondrial calcium uniporter (MCU) reaches 3 mM/s, compatible with available literature. TEM images of calcium entry units and Mn2+ quenching showed a greater capacity of store-operated calcium entry in KO compared to WT. However, levels of [Ca2+]cyto during tetanic stimulation were not modulated to variations of extracellular calcium.<BR><B>CONCLUSIONS: </B>The model-based analysis of experimentally determined calcium distribution during tetanic stimulation showed that mitochondria can act as a buffer to compensate for the lack of PV. This result contributes to a better understanding of mitochondria's role in modulating [Ca2+]cyto in skeletal muscle fibers.