ATP-SENSITIVE K+ CHANNEL BLOCKER GLIBENCLAMIDE AND DIAPHRAGM FATIGUE DURING NORMOXIA AND HYPOXIA

The role of ATP-sensitive K+ channels in skeletal muscle contractile p erformance is controversial: blockers of these channels have been foun d to not alter, accelerate, or attenuate fatigue. The present study re examined whether glibenclamide affects contractile performance during repetitive contraction. Experiments systematically assessed the effect s of stimulation paradigm, temperature, and presence of hypoxia and in addition compared intertrain with intratrain fatigue. Adult rat diaph ragm muscle strips were studied in vitro. At 37 degrees C and normoxia , glibenclamide did not significantly affect any measure of fatigue du ring continuous 5- or 100-Hz or intermittent 20-Hz stimulation but pro gressively prolonged relaxation time during 20-Hz stimulation. At 20 d egrees C and normoxia, neither force nor relaxation rate was affected significantly by glibenclamide during 20-Hz stimulation. At 37 degrees C and hypoxia, glibenclamide did not significantly affect fatigue at 5-Hz or intertrain fatigue during 20-Hz stimulation but reduced intrat rain fatigue and prolonged relaxation time during 20-Hz stimulation. T hese findings indicate that, although ATP-sensitive K+ channels may be activated during repetitive contraction, their activation has only a modest effect on the rate of fatigue development.