The effects of glibenclamide on tetanic force and intracellular calcium in normal and fatigued mouse skeletal muscle.
In this study the effects of ATP-sensitive K+ channel modulators were studied in intact single fibres dissected from mouse skeletal muscle. Indo-1 was used to measure [Ca2+]i simultaneously with force during normal and fatiguing stimulation. In control fibres, opening of ATP-sensitive K+ channels with BRL 38227 produced a small reduction in tetanic force and [Ca2+]i. In contrast, glibenclamide, a selective blocker of the ATP-sensitive K+ channel, slightly increased tetanic force and [Ca2+]i in these fibres and also increased Ca2+ sensitivity. Glibenclamide produced a more marked increase in tetanic force and [Ca2+]i during the later stages of fatiguing stimulation, although this effect was observed in only 50% of fibres examined. We conclude from this study that glibenclamide produces a partial reversal of the later stages of fatigue in a subpopulation of muscle fibres. Opening of ATP-sensitive K+ channels may therefore contribute to the decline in tetanic force and [Ca2+]i characteristic of skeletal muscle fatigue.
Duty
S
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Department of Physiology, University of Sydney, NSW, Australia.
Allen
D G
DG
D000138:Acidosis / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D019806:Cromakalim; D004558:Electric Stimulation; D005905:Glyburide / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D018763:Muscle Fatigue / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D012016:Reference Values
D001578:Benzopyrans; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D000255:Adenosine Triphosphate; D005905:Glyburide; D002118:Calcium