Effects of Carbohydrate Availability on Fatigue and Fatigue Pre-Conditioning in Mouse FDB Muscle

Abstract

To prevent damaging ATP depletion during periods of intense activity‚ intrinsic mechanisms within skeletal muscle are activated and lead to myoprotection; a process known as muscle fatigue. It has been proposed that the primary mechanism of fatigue is a submaximal sarcoplasmic reticulum Ca2+ release and decreased force generation‚ however‚ what triggers this mechanism remains controversial. It is possible that glycogen may act as a trigger as studies have repeatedly shown a direct correlation between glycogen content at the beginning of activity and time to fatigue. In previous studies‚ a fatigue bout and/or period of fasting to deplete glycogen was used. However, this leaves investigators to differentiate between the effects of glycogen depletion methodology causing a metabolic stress and effects of glycogen itself. One objective of this M.Sc. project was to produce a low glycogen model without a prior metabolic stress that could forgo these limitations. It was extended to differentiate between the role of glycogen and extracellular glucose during fatigue as well as fatigue pre-conditioning (FPC)‚ a phenomenon in which fatigue resistance increases for about 2 hours after a first fatigue bout. During a single‚ first fatigue bout (one contraction every sec for 3 min) a mean decrease in glycogen from 95 to 20 μmol/g dry wt. had no effect on the decrease in tetanic [Ca2+]i‚ i.e. the [Ca2+]i during tetanic contractions‚ whereas removing glucose from the physiological solution led to a 46% greater decrease in tetanic [Ca2+]i than when glucose was present. During a subsequent fatigue bout (i.e. FPC) a greater amount of glycogen was used as glycogen content was 27% greater than prior to the first fatigue bout. When glycogen and/or glucose was limited‚ FPC was abolished. It is concluded that extracellular glucose is critical to prevent fatigue. Additionally, whereas glycogen is important for FPC‚ it appears to be much less important during a first fatigue bout initiated in absence of any prior metabolic stress.