Prolonged aerobic exercise: physiological studies in rat gastrocnemius with additional observations on the effects of acute mitochondrial blockade.
Protracted low frequency (1 and 5 Hz) stimulation of rat gastrocnemius in vivo leads to fatigue and fall out of glycolytic fibres with the development of a stable twitch response with continuation of the stimulus train. This model was used to examine the physiological effects of acute mitochondrial blockade on oxidative fibre function with the injection of a mitochondrial uncoupler (dinitrophenol) and a site I inhibitor (diphenyleneiodonium) intraarterially after a stable twitch response had developed. Dinitrophenol leads to progressive failure of contractility, closely followed by action potential failure and electrically silent contracture: external work accelerated this sequence but it also developed in resting muscle suggesting that DNP lead to active ATP hydrolysis and a more severe energy depletion than that encountered in human disease states. Diphenyleneiodonium also leads to progressive twitch tension and action potential failure but contracture was late and inconstant, considerable recovery in twitch parameters was seen with rest and restimulation lead to pathological fatiguability of twitch tension. This model has some similarity to human mitochondriopathies with pathological fatiguability. This acute model should allow ready testing of any therapeutic approaches which bypass respiratory chain blocks.
Byrne
E
E
Institute of Neurology, Queen Square, London, U.K.
Morgan Hughes
J A
JA
D000818:Animals; D004140:Dinitrophenols / Q000494:pharmacology*; D004558:Electric Stimulation; D004734:Energy Metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000378:metabolism / Q000502:physiology*; D009861:Onium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D004140:Dinitrophenols; D009861:Onium Compounds; C007517:diphenyleneiodonium