Role Of KATP Channels During Fatigue And Metabolic Inhibition In Chicken Slow Skeletal Muscle

Abstract

The slow-twitch muscle fibers in contrast to the fast-twitch muscle fibers are fatigue-resistant. During fatiguing exercise, the ATP cost of contraction is reduced. This reduction in ATP can be sensed by KATP channels (ATP-sensitive potassium channels), which couple the metabolic state of the cell to its electric activity, causing its activation. Therefore, it has been proposed that KATP participate in fatigue in the fast-twitch skeletal muscle besides to ischemia in nervous system. In slow-twitch muscle fibers there are few studies related to muscle fatigue phenomena. Thus, in this study we designed an in vitro model for fatigue in chicken slow-twitch skeletal muscle to investigate the role of KATP channels in the fatigue process. We studied the effects of glibenclamide, which blocks KATP channels, on twitch and tetanus tension in the anterior latissimus dorsi slow muscle induced to fatigue. The results show that glibenclamide increases tension in the fatigued muscle. Also, the slow muscle was exposed to metabolic poisoning by cyanide, a condition in which the ATP formation is inhibited and when its intracellular concentration is diminished KATP channels are activated which in turn produces a reduction in muscle tension. The addition of glibenclamide in these conditions abolished the effect produced by cyanide. Moreover, we studied the possible role of intracellular calcium by studying the effects of glibenclamide on the contractures evoked by caffeine, which is known that releases calcium from sarcoplasmic reticulum. In these conditions glibenclamide increases tension. Thus, we are showing evidences of the role of KATP channels in the fatigue process, since glibenclamide increases twitch and tetanus tension in chicken fatigued slow muscle and during metabolic inhibition. These effects could be mediated by an increase in the calcium release from sarcoplasmic reticulum.