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Article Dans Une Revue Biochemical Journal Année : 2009

Modular regulation analysis of integrative effects of hypoxia on the energetics of contracting skeletal muscle in vivo

Christophe Beuste
  • Fonction : Auteur
Sylvain Miraux
Véronique Deschodt-Arsac
Eric Thiaudiere
  • Fonction : Auteur
Jean-Michel Franconi
  • Fonction : Auteur
Philippe H Diolez
  • Fonction : Auteur

Résumé

In exercising muscle, acute reduction in ambient oxygen impairs muscle contraction due to effects of hypoxia on mitochondrial ATP supply. The less marked impairment reported after long-term exposure to hypoxia points to changes in regulation of the energetic system of contraction in hypoxic conditioned animals. This energetic system was conceptually defined here as two modules, ATP/PCr-producer and ATP/PCr-consumer connected by energetic intermediates. Modular control analysis (MoCA) that combines top-down control analysis with non-invasive 31P-NMR spectroscopy was used to describe in vivo the effects of hypoxia and adaptation to hypoxia on each module. Modulations of steady levels of ATP turnover (indirectly assessed as force output) and muscle PCr were obtained in hypoxic conditioned (HC) rats (6 weeks at 10.5% O2) vs. normoxic (N) rats. Modular control and regulation analyses quantified the elasticity to PCr of each module in N and HC rats as well as the direct effect of acute hypoxia on the PCr/ATP-producer module. Similar elasticities in N and HC rats indicate the absence of response to long-term hypoxia in internal regulations of the ATP supply and demand pathways. The less marked impairment of contraction by acute hypoxia in HC rats (-9±6% vs. -17±14% in N rats, P<0.05) was therefore fully explained by a lower direct effect (HC -31±13% vs. N -44±23%, P<0.05) of acute hypoxia on mitochondrial ATP supply. This points up a positive adaptation to chronic hypoxia. MoCA in vivo may provide powerful tools to find out improved function (alternatively dysfunction) at system level in conditioned animals.

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Dates et versions

hal-00479138 , version 1 (30-04-2010)

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Christophe Beuste, Sylvain Miraux, Véronique Deschodt-Arsac, Eric Thiaudiere, Jean-Michel Franconi, et al.. Modular regulation analysis of integrative effects of hypoxia on the energetics of contracting skeletal muscle in vivo. Biochemical Journal, 2009, 420 (1), pp.67-72. ⟨10.1042/BJ20082385⟩. ⟨hal-00479138⟩

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