title: Lactate is a metabolic substrate that sustains extraocular muscle function.
abstract: Lactic acid is considered the end product of glycolysis and is a major cause of muscle fatigue. However, the lactate dehydrogenase (LDH) reaction is bidirectional: Lactate can be oxidized to pyruvate and used as a substrate for the Krebs cycle. Therefore, our hypothesis was that lactate sustains the contractile function of rat extraocular muscles during periods of increased activity. The study used extraocular and extensor digitorum longus (EDL) muscles from adult Sprague-Dawley rats to determine LDH isoform expression, total LDH activity, and contractile function in vitro. To evaluate the role of lactate on fatigue, we tested the effect of cinnamate, a blocker of lactate transport, and exogenous lactate on fatigue resistance. Cinnamate accelerated fatigue in the extraocular muscles: Endurance and residual force decreased significantly. Conversely, cinnamate did not affect the endurance or residual force of EDL muscles. Replacing glucose with exogenous lactate increased EDL fatigability but had no effect on the extraocular muscles. However, the extraocular muscles fatigued faster when exposed to exogenous lactate combined with cinnamate. The LDH-A and LDH-C isoforms were expressed at lower levels in extraocular muscle; LDH-B was equally abundant in the EDL and extraocular muscles. Total LDH activity in the extraocular muscles was only approximately 32% of the level in EDL. These results support the hypothesis that lactate sustains the contractile performance of the extraocular muscles.
authors.affiliation: Department of Physiology, University of Kentucky, 800 Rose St., Lexington, KY 40536-0298, USA. paco.andrade@uky.edu
authors.forename: Francisco H
authors.initials: FH
authors.lastname: Andrade
authors.forename: Colleen A
authors.initials: CA
authors.lastname: McMullen
mesh_terms: D000818:Animals; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D018763:Muscle Fatigue / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009801:Oculomotor Muscles / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019344:Lactic Acid