EFFECT OF TOLBUTAMIDE ON THE RATE OF FATIGUE AND RECOVERY IN FROG SARTORIUS MUSCLE

The goal of this study was to determine how blocking ATP-sensitive Kchannels with tolbutamide affects the excitability and contractility o f intact frog sartorius muscle during fatigue development. Fatigue was elicited with one tetanic contraction every sec for 3 min. During fat igue the resting potential decreased by 10 mV although the action pote ntial overshoot remained constant. The addition of 2 mmol . liter(-1) tolbutamide 60 min before fatigue did not modify the effect of fatigue on the resting potential and action potential overshoot. During fatig ue development the half-repolarization time of control muscles increas ed by 0.26 msec in control muscles, although it increased by 0.77 msec in the presence of 2 mmol . liter(-1) tolbutamide; the difference was significant, The decrease in force during fatigue development was not affected by 2 mmol . liter(-)1 tolbutamide (added 60 min before fatig ue), whereas the recovery of force after fatigue was slower in tolbuta mide- exposed muscles than in control muscles. Addition of 2 mmol . li ter(-)1 tolbutamide after 5 min of recovery reduced the recovery rate of the resting potential and half-repolarization time, but did not aff ect the recovery of tetanic force during the first 40 min. Our results are consistent with the hypothesis that ATP-sensitive K+ channels are activated during fatigue development and that they contribute to the repolarization phase of action potentials, but they do not support the hypothesis that ATP-sensitive K+ channels contribute to the decrease in force.