The effects of glibenclamide on tetanic force and intracellular calcium in normal and fatigued mouse skeletal muscle

Abstract

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.