ATP-sensitive K+ channel blocker glibenclamide and diaphragm fatigue during normoxia and hypoxia.
The role of ATP-sensitive K+ channels in skeletal muscle contractile performance is controversial: blockers of these channels have been found to not alter, accelerate, or attenuate fatigue. The present study reexamined whether glibenclamide affects contractile performance during repetitive contraction. Experiments systematically assessed the effects of stimulation paradigm, temperature, and presence of hypoxia and in addition compared intertrain with intratrain fatigue. Adult rat diaphragm muscle strips were studied in vitro. At 37 degrees C and normoxia, glibenclamide did not significantly affect any measure of fatigue during continuous 5- or 100-Hz or intermittent 20-Hz stimulation but progressively prolonged relaxation time during 20-Hz stimulation. At 20 degrees 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 intratrain fatigue and prolonged relaxation time during 20-Hz stimulation. These 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.
Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA. exv4@po.cwru.edu
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Van Lunteren
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Moyer
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Torres
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D005905:Glyburide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature
D007004:Hypoglycemic Agents; D026902:Potassium Channel Blockers; D000255:Adenosine Triphosphate; D005905:Glyburide