ATP-sensitive K+ channel blocker glibenclamide and diaphragm fatigue during normoxia and hypoxia

The role of ATP-sensitiveK⁺ channels in skeletal musclecontractile performance is controversial: blockers of these channels have been found to not alter, accelerate, or attenuate fatigue. Thepresent study reexamined whether glibenclamide affects contractile performance during repetitive contraction. Experiments systematically assessed the effects of stimulation paradigm, temperature, and presenceof hypoxia and in addition compared intertrain with intratrain fatigue.Adult rat diaphragm muscle strips were studied in vitro. At 37°Cand normoxia, glibenclamide did not significantly affect any measure offatigue during continuous 5- or 100-Hz or intermittent 20-Hzstimulation but progressively prolonged relaxation time during 20-Hzstimulation. At 20°C and normoxia, neither force nor relaxationrate was affected significantly by glibenclamide during 20-Hzstimulation. At 37°C and hypoxia, glibenclamide did notsignificantly affect fatigue at 5-Hz or intertrain fatigue during 20-Hzstimulation but reduced intratrain fatigue and prolonged relaxationtime during 20-Hz stimulation. These findings indicate that, althoughATP-sensitive K⁺ channels may beactivated during repetitive contraction, their activation has only amodest effect on the rate of fatigue development.