[The role of the mitochondrial permeability transition pore in the development of skeletal muscle fatigue in dogs].

On anaesthetized dogs the role of the mitochondrial permeability transition pore (mPTP) in the development of the m. gastrocnemius fatigue was investigated. In a control series of experiments it was shown, that 10 short-term (30") electrical stimulation (8 Hz, 5 ms, 20 V) with 5" interval resulted in significant reduction of the muscle contractions force (more than 40%) and considerably increased oxygen cost of a m. gastrocnemicus work (more than 130%), comparison with initial parameters. The registered inhibition of the muscle contraction force pointed on the development of m. gastrocnemius fatigue, that was accompanied by an appearance in blood from v. femoralis mitochondrial factor (MF), which, as shown by us earlier, is a marker of the mPTP opening. Preliminary injection of selective inhibitor of the mPTP opening cyclosporine A (0.012 mg/kg, i.v.) resulted in the pronounced fall of the MF concentration in blood from v. femoralis, in comparison with the parameters registered under control conditions. Pretreatment with the another inhibitor of the mPTP opening melatonin (0.75 mg/kg, i.v.) prevented inhibition of the muscle contractions force and reduction of the efficiency of oxygen using by m. gastercnemicus under conditions similar control. Thus, m. gastercnemius fatigue didn't develop, and the MF concentration in blood from v. femoralis was much lower, than in the control, that testified to absence of the mPTP opening. So then, fatigue development was accompanied by inhibition of the muscle contractions force, marked reduction of the efficiency of oxygen using by m.gastercnemicus that was prevented by the mPTP opening inhibitors. Thus, the mPTP opening can underlie the development of the working skeletal muscle fatigue.