Experimentally Induced Defects of Mitochondrial Metabolism in Rat Skeletal Muscle. Biological Effects of the NADH: Coenzyme Q Reductase Inhibitor Diphenyleneiodonium

Overview

Journal Biochem J

Specialty Biochemistry

Date 1985 Jul 1

PMID 3929766

Citations 2

Authors

D J Hayes

E Byrne

E A Shoubridge

J A Morgan-Hughes

J B Clark

Affiliations

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Abstract

An animal model for the human condition of mitochondrial myopathy has been established and characterized physiologically and biochemically. The NADH: coenzyme Q reductase inhibitor diphenyleneiodonium [Bloxham (1979) Biochem. Soc. Trans. 7, 103-106] was either infused acutely in vivo into rat hind limb or injected chronically into rats. Both modes of delivery resulted in a reduced muscle oxidative capacity and increased fatigue. Analysis of muscle metabolites by h.p.l.c. and 31P-n.m.r. indicated that ATP concentrations were similar to control values during periods of stimulation and these were maintained by the phosphocreatine pool. During the recovery period after muscle stimulation in the experimental animals the muscle pH remained depressed and the rate of phosphocreatine synthesis was markedly delayed as compared with controls. Factors thought to be involved in the fatigue response are discussed in relation to this model.

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