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EXERCISE AND RESPIRATORY PHYSIOLOGY

Resistance to Ca²⁺-induced opening of the permeability transition pore differs in mitochondria from glycolytic and oxidative muscles

¹Département de kinésiologie, Université de Montréal, Montreal, Quebec; and ²Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec, Canada

Submitted 15 April 2008 ; accepted in final form 16 May 2008

This study determined whether susceptibility to opening of the permeability transition pore (PTP) varies according to muscle phenotype represented by the slow oxidative soleus (Sol) and superficial white gastrocnemius (WG). Threshold for Ca²⁺-induced mitochondrial Ca²⁺ release following PTP opening was determined with a novel approach using permeabilized ghost myofibers. Threshold values for PTP opening were approximately threefold higher in fibers from WG compared with those from Sol (124 ± 47 vs. 30.4 ± 6.8 pmol Ca²⁺/mU citrate synthase). A similar phenomenon was also observed in isolated mitochondria (threshold: 121 ± 60 vs. 40 ± 10 nmol Ca²⁺/mg protein in WG and Sol), indicating that this was linked to differences in mitochondrial factors between the two muscles. The resistance of WG fibers to PTP opening was not related to the expression of putative protein modulators (cyclophilin D, adenylate nucleotide translocator-1, and voltage-dependent anion channels) or to difference in respiratory properties and occurred despite the fact that production of reactive oxygen species, which promote pore opening, was higher than in the Sol. However, endogenous matrix Ca²⁺ measured in mitochondria isolated under resting baseline conditions was approximately twofold lower in the WG than in the Sol (56 ± 4 vs. 111 ± 11 nmol/mg protein), which significantly accounted for the resistance of WG. Together, these results reveal fiber type differences in the sensitivity to Ca²⁺-induced PTP opening, which may constitute a physiological mechanism to adapt mitochondria to the differences in Ca²⁺ dynamics between fiber types.

skeletal muscle; fiber phenotype

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