Editing Muscle fatigue (section)

===Metabolites===
Metabolites are the substances (generally waste products) produced as a result of muscular contraction.  They include [[chloride]], [[potassium]], [[lactic acid]], [[Adenosine diphosphate|ADP]], [[magnesium]] (Mg<sup>2+</sup>), [[reactive oxygen species]], and [[inorganic phosphate]].  Accumulation of metabolites can directly or indirectly produce metabolic fatigue within muscle fibers through interference with the release of calcium (Ca<sup>2+</sup>) from the sarcoplasmic reticulum or reduction of the sensitivity of contractile molecules [[actin]] and [[myosin]] to calcium.

====Chloride====
Intracellular [[chloride]] partially inhibits the contraction of muscles. Namely, it prevents muscles from contracting due to "false alarms", small stimuli which may cause them to contract (akin to [[myoclonus]]).

====Potassium====
High concentrations of [[potassium]] (K<sup>+</sup>) also causes the muscle cells to decrease in efficiency, causing cramping and fatigue. Potassium builds up in the [[t-tubule]] system and around the muscle fiber as a result of [[action potentials]]. The shift in K<sup>+</sup> changes the membrane potential around the muscle fiber. The change in membrane potential causes a decrease in the release of [[calcium]] (Ca<sup>2+</sup>) from the [[sarcoplasmic reticulum]].<ref name="Silverthorne2009">{{cite book|author=Dee Unglaub Silverthorn|title=Human Physiology: An Integrated Approach|year=2009|publisher= Pearson|edition = 5th|isbn= 978-0321559807|page=412}}</ref>

====Lactic acid====
It was once believed that [[lactic acid]] build-up was the cause of muscle fatigue.<ref name="pmid3471061">{{cite journal | vauthors = Sahlin K | title = Muscle fatigue and lactic acid accumulation | journal = Acta Physiol Scand Suppl | volume = 556 | pages = 83–91 | date = 1986 | pmid = 3471061 }}</ref>  The assumption was lactic acid had a "pickling" effect on muscles, inhibiting their ability to contract.  Though the impact of lactic acid on performance is now uncertain, it may assist or hinder muscle fatigue.

Produced as a by-product of [[lactic acid fermentation|fermentation]], lactic acid can increase intracellular acidity of muscles.  This can lower the sensitivity of contractile apparatus to Ca<sup>2+</sup> but also has the effect of increasing [[cytoplasm]]ic Ca<sup>2+</sup> concentration through an inhibition of the [[sodium-calcium exchanger|chemical pump]] that [[Active transport|actively transports]] calcium out of the cell.  This counters inhibiting effects of potassium on muscular action potentials.  Lactic acid also has a negating effect on the chloride ions in the muscles, reducing their inhibition of contraction and leaving potassium ions as the only restricting influence on muscle contractions, though the effects of potassium are much less than if there were no lactic acid to remove the chloride ions.  Ultimately, it is uncertain if lactic acid reduces fatigue through increased intracellular calcium or increases fatigue through reduced sensitivity of contractile proteins to Ca<sup>2+</sup>.

Lactic acid is now used as a measure of endurance training effectiveness and [[VO2 max|VO<sub>2</sub> max]].<ref name="pmid26136542">{{cite journal | vauthors = Lundby C, Robach P | title = Performance Enhancement: What Are the Physiological Limits? | journal = Physiology | volume = 30 | issue = 4 | pages = 282–92 | date = July 2015 | pmid = 26136542 | doi = 10.1152/physiol.00052.2014 | s2cid = 36073287 }}</ref>