Rat diaphragm mitochondria have lower intrinsic respiratory rates than mitochondria in limb muscles

Abstract

Garcia-Cazarin ML, Gamboa JL, Andrade FH. Rat diaphragm mitochondria have lower intrinsic respiratory rates than mitochondria in limb muscles. Am J Physiol Regul Integr Comp Physiol 300: R1311-R1315, 2011. First published March 9, 2011 doi:10.1152/ajpregu.00203.2010.-The mitochondrial content of skeletal muscles is proportional to activity level, with the assumption that intrinsic mitochondrial function is the same in all muscles. This may not hold true for all muscles. For example, the diaphragm is a constantly active muscle; it is possible that its mitochondria are intrinsically different compared with other muscles. This study tested the hypothesis that mitochondrial respiration rates are greater in the diaphragm compared with triceps surae (TS, a limb muscle). We isolated mitochondria from diaphragm and TS of adult male Sprague Dawley rats. Mitochondrial respiration was measured by polarography. The contents of respiratory complexes, uncoupling proteins 1, 2, and 3 (UCP1, UCP2, and UCP3), and voltage-dependent anion channel 1 (VDAC1) were determined by immunoblotting. Complex IV activity was measured by spectrophotometry. Mitochondrial respiration states 3 (substrate and ADP driven) and 5 (uncoupled) were 27 Ϯ 8% and 24 Ϯ 10%, respectively, lower in diaphragm than in TS (P Ͻ 0.05 for both comparisons). However, the contents of respiratory complexes III, IV, and V, UCP1, and VDAC1 were higher in diaphragm mitochondria (23 Ϯ 6, 30 Ϯ 8, 25 Ϯ 8, 36 Ϯ 15, and 18 Ϯ 8% respectively, P Յ 0.04 for all comparisons). Complex IV activity was 64 Ϯ 16% higher in diaphragm mitochondria (P Յ 0.01). Mitochondrial UCP2 and UCP3 content and complex I activity were not different between TS and diaphragm. These data indicate that diaphragm mitochondria respire at lower rates, despite a higher content of respiratory complexes. The results invalidate our initial hypothesis and indicate that mitochondrial content is not the only determinant of aerobic capacity in the diaphragm. We propose that UCP1 and VDAC1 play a role in regulating diaphragm aerobic capacity. respiratory muscles; triceps surae; mitochondria respiration; uncoupling proteins DURING PERIODS OF SUSTAINED physical activity, O 2 consumption is driven mostly by mitochondrial respiration in skeletal muscles, since ATP demand is met by aerobic metabolism (26). Skeletal muscle mitochondrial volume density is a good predictor for V O 2max (26,28). In turn, the general concept is that the more active muscles have higher mitochondria content to meet their potentially greater metabolic demands (17, 28). In mammals, this concept usually excludes the possibility that there might be intrinsic differences in mitochondrial function among skeletal muscles, in particular those muscles with more extreme activation patterns. This is not the case in other vertebrates. For example, hummingbird flight muscles have greater mitochondrial volume density and capillary surface to muscle fiber surface than most, if not all, mammalian skeletal muscles, as befits their fast and sustained activit...

ERS statement on respiratory muscle testing at rest and during exercise

“…In rats, mitochondrial respiratory rates are lower in the diaphragm than in peripheral muscles [281]. In mice, hypoxia differentially affected peripheral and respiratory muscles with decreased mitochondrial content due to reduced mitochondrial biogenesis and increased mitophagy [282].…”

Increased AMP-activated protein kinase in skeletal muscles of Murphy Roth Large mice and its potential role in altered metabolism

“…VDAC is located on the outer mitochondrial membrane. Although variably expressed between tissue types (Garcia-Cazarin et al 2011), it appears to be uniformly expressed within skeletal muscles (Taub et al 2012), and is therefore a valid surrogate marker for mitochondrial density (Jahnke et al 2012).…”

Respiratory muscle dysfunction in animal models of hypoxic disease: antioxidant therapy goes from strength to strength

“… 106 Exercise leads to improved diaphragm 107 , 108 and upper airway 109 muscle endurance, resulting from increased aerobic capacity. Increased endurance 7 and mitochondrial efficiency 73 , 89 in diaphragm, which differs to responses in limb muscles, 73 , 110 , 111 might relate to differences in activation patterns as well as intrinsic differences in muscle form. Thus, one could argue that activity-induced plasticity might limit the deleterious effects of hypoxic stress.…”