Effect of the opener Diazoxide and the inhibitor 5‐Hidroxidecanoate of the mitochondrial KATP channel in the fatigue of slow skeletal muscle

Abstract

Fatigue is the reduction in physical strength or a flaw in the maintenance of energy production (Allen et al., 2008). Garcia et al. (2009) showed that the mitoKATP plays an important role in protecting the muscle during fatigue. Thus, the intent of this study was to determine the involvement of mitochondrial KATP channels in the muscle fatigue process to explore the effect of diazoxide and 5-Hidroxidecanoate (5-HD) on the tension chicken slow skeletal muscle in a in vitro model of fatigue. We used the Latissimus Dorsi muscle (ALD) of chicks, between 1 and 3 weeks old. The muscle was mounted on an experimental recording chamber by placing the proximal end to the bottom of the chamber and the distal end to hook of the mechanoelectric transducer (Grass FT03), which through a CyberAmp amplifier 320 and a Digidata (1322A) and finall to a computer (Pentium 4) the software of data acquisition was AXOTAPE, PClamp 9.2. We performed a fatigue protocol by inducing twitches by repetitive electrical stimulation (pulses of 100 Volts, 300 ms duration, frequency of 0.2 Hz). The muscle was stimulated until the force decreased by 70%, then we applied the study drug for 6 min to observe its effect. We used diazoxide (30 μM) and 500 μM for 5-HD, respectively. The application of Diazoxide (30 μM) increases postfatigue tension by 40.7% while in the presence of 5-HD we observe no change (reduction) statistically significantly. We believe that the null effect of 5-HD might be related to the metabolism of the drug and its lack of specificity.