This study explores the importance of creatine kinase (CK) in the regulation of muscle mitochondrial respiration in human subjects depending on their level of physical activity. Volunteers were classified as sedentary, active or athletic according to the total activity index as determined by the Baecke questionnaire in combination with maximal oxygen uptake values (peak ◊ O 2 , expressed in ml min _1 kg _1 ). All volunteers underwent a cyclo-ergometric incremental exercise test to estimate their peak ◊ O 2 and ◊ O 2 at the ventilatory threshold (VT). Muscle biopsy samples were taken from the vastus lateralis and mitochondrial respiration was evaluated in an oxygraph cell on saponin permeabilised muscle fibres in the absence (◊ 0 ) or in the presence (◊ max ) of saturating [ADP]. While ◊ 0 was similar, ◊ max differed among groups (sedentary, 3.7 ± 0.3, active, 5.9 ± 0.9 and athletic, 7.9 ± 0.5 mmol O 2 min _1 (g dry weight)
_1). ◊ max was correlated with peak ◊ O 2 (P < 0.01, r = 0.63) and with ◊ T (P < 0.01, r = 0.57). There was a significantly greater degree of coupling between oxidation and phosphorylation (◊ max /◊ 0 ) in the athletic individuals. The mitochondrial K m for ADP was significantly higher in athletic subjects (P < 0.01). Mitochondrial CK (mi-CK) activation by addition of creatine induced a marked decrease in K m in athletic individuals only, indicative of an efficient coupling of mi-CK to ADP rephosphorylation in the athletic subjects only. It is suggested that increasing aerobic performance requires an enhancement of both muscle oxidative capacity and mechanisms of respiratory control, attesting to the importance of temporal co-ordination of energy fluxes by CK for higher efficacy.
Activation of the transcription factor nuclear factor of activated T cells by the calcium-sensitive serine/threonine phosphatase calcineurin has been proposed as one of the molecular mechanisms by which motor nerve activity establishes the slow muscle phenotype. To investigate whether the calcineurin pathway can regulate the large spectrum of slow muscle characteristics in vivo, we treated rats for three weeks with cyclosporin A (an inhibitor of calcineurin). In soleus (slow muscle), but not in plantaris (fast muscle), the proportion of slow myosin heavy chain (MHC-1) and slow sarcoplasmic reticulum ATPase (SERCA2a) was decreased, whereas that of fast MHC (MHC-2A) and fast SERCA1 increased, indicating a slow to fast contractile phenotype transition. Cytosolic isoforms of creatine kinase and lactate dehydrogenase (most abundant in fast fibers), as well as mitochondrial creatine kinase and citrate synthase activities (elevated in fast/oxidative fibers) were dose dependently increased by cyclosporin A treatment in soleus muscle, with no change in plantaris. Calcineurin catalytic subunit was more abundant in soleus muscle fibers compared with plantaris. Taken together these results suggest that the calcineurin pathway co-regulates a set of multigenic protein families involved in the transition between slow oxidative (type I) to fast oxidative (type IIa) phenotype in soleus muscle.
In these patients, the disease-specific muscle metabolic impairments derive mostly from extramitochondrial mechanisms that disrupt the normal symmorphosis relations. The possible roles of ACE inhibitors and level of activity are discussed.
This study investigated the effects of voluntary wheel running on the myosin heavy chain (MHC) composition of the soleus (Sol) and plantaris muscles (Pla) in rats developing under hypobaric choronic hypoxia (CH) conditions during 4 wk in comparison with those of control rats maintained under local barometric pressure conditions (C) or rats pair-fed an equivalent quantity of food to that consumed by CH animals (PF). Compared with C animals, sedentary rats subjected to CH conditions showed a significant decrease in type I MHC in Sol (-12%, P < 0.01). Although strongly decreased under hypoxia, spontaneous running activity increased the expression of type I MHC (P < 0.01) so that no difference in the MHC profile of Sol was shown between CH active and C active rats. The MHC distribution in Sol of PF rats was not significantly different from that found in C animals. CH resulted in a significant decrease in type I (P < 0.01) and type IIA (P < 0.005) MHC, concomitant with an increase in type IIB MHC in Pla (P < 0.001), compared with C and PF animals. In contrast to results in Sol muscle, this slow-to-fast shift in the MHC profile was unaffected by spontaneous running activity. These results suggest that running exercise suppresses the hypoxia-induced slow-to-fast transition in the MHC expression in Sol muscles only. The hypoxia-induced decrease in food intake has no major influence on MHC expression in developing rats.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.