Pinacidil suppresses contractility and preserves energy but glibenclamide has no effect during muscle fatigue

The effects of 10 mu M glibenclamide, an ATP-sensitive K+ (K-ATP) channel b locker, and 100 mu M pinacidil, a channel opener, were studied to determine how the K-ATP channel affects mouse extensor digitorum longus (EDL) and so leus muscle during fatigue. Fatigue was elicited with 200-ms-long tetanic c ontractions every second. Glibenclamide did not affect rate and extent of f atigue, force recovery, or Rb-86(+) fractional loss. The only effects of gl ibenclamide during fatigue were: an increase in resting tension (EDL and so leus), a depolarization of the cell membrane, a prolongation of the repolar ization phase of action potential, and a greater ATP depletion in soleus. P inacidil, on the other hand, increased the rate but not the extent of fatig ue, abolished the normal increase in resting tension during fatigue, enhanc ed force recovery, and increased Rb-86(+) fractional loss in both the EDL a nd soleus. During fatigue, the decreases in ATP and phosphocreatine of sole us muscle were less in the presence of pinacidil. The glibenclamide effects suggest that fatigue, elicited with intermittent contractions, activates f ew K-ATP channels that affect resting tension and membrane potentials but n ot tetanic force, whereas opening the channel with pinacidil causes a faste r decrease in tetanic force, improves force recovery, and helps in preservi ng energy.