Effects of fatigue of rat EDL in situ on metabolism of phosphoinositides.

The study was conducted to determine the effect of persistent fatigue in situ on the inositol phosphate second messenger system proposed to constitute a step in excitation-contraction coupling. Rat EDL, after stimulation in situ for 1 hr (100 Hz for 330 ms, 1/s), showed increased incorporation of myo-[3H]inositol into membrane phosphoinositides during a subsequent 4-h incubation period. The rate of hydrolysis of this pool resulting from 10 sec of tetanic stimulation, as well as the rate of production of inositol phosphates InsP, InsP2, and InsP3, were significantly reduced in fatigued muscles. These results suggest that the metabolic changes that parallel the alteration in contractile response with fatigue reflect a disruption in E-C coupling.