Abstract
Abstract: :
Purpose: Traditionally, lactate has been considered an end product of glycolysis and a major cause of muscle fatigue during exercise. However, the lactate dehydrogenase (LDH) reaction is bidirectional, and muscles may use it to generate pyruvate, a substrate for aerobic metabolism. The extraocular muscles (EOMs) are characterized by high oxidative capacity and fatigue resistance. Therefore, the purpose of this study was to determine if lactate influx into EOMs is an important mechanism to sustain contractile function during periods of increased activity. Methods: Intact EOMs and extensor digitorum longus muscles (EDL, prototypical fast limb muscle) were isolated from 90–day old male Sprague–Dawley rats for quantitative PCR (qPCR) of LDH isoforms and functional studies in vitro. Baseline isometric contractile properties and fatigue resistance of whole EOMs and small EDL bundles were determined with and without α–cyano–4–hydroxycinnamic acid, a blocker of lactate transport (cinnamate, 5 mM). Results: Cinnamate had a small effect on maximal force production by EOMs and EDL muscle bundles (6±2 and 8±2% decreases vs. baseline, respectively, P < 0.05). As expected, EDL muscle bundles fatigued faster than EOMs, as evidenced by a shorter time to reach a target decline in force during the fatigue protocol. Cinnamate rendered EOMs more fatigable: endurance decreased from 600 to 458±36 seconds (control vs. cinnamate, P< 0.01) and residual force decreased from 62±5 to 31±8% of initial force (control vs. cinnamate, P< 0.01). On the other hand, EDL was more resistant to cinnamate: endurance was not affected, and residual force decreased from 43±5 to 38±2% of initial (control vs. cinnamate, P<0.05). qPCR demonstrated that LDH–A and –B, the major isoforms in skeletal muscle, were expressed at equivalent levels in EOM and EDL. Conclusions: These results support our original premise that lactate influx into EOMs delays the progression of fatigue during periods of increased activity. However, we failed to demonstrate that EOMs have increased expression of LDH–B, the isoform associated with conversion of lactate to pyruvate. This suggests that compartmentalization of LDH activity may be critical to achieve the observed effect on fatigue resistance.
Keywords: extraocular muscles: structure • metabolism • enzymes/enzyme inhibitors