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Am J Physiol Regul Integr Comp Physiol ; 294(4): R1347-55, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18305024

ABSTRACT

Muscle fatigue is associated with a number of clinical diseases, including chronic pain conditions. Decreases in extracellular pH activates acid-sensing ion channel 3 (ASIC3), depolarizes muscle, protects against fatigue, and produces pain. We examined whether ASIC3-/- mice were more fatigable than ASIC3+/+ mice in a task-dependent manner. We developed two exercise protocols to measure exercise-induced muscle fatigue: (fatigue task 1, three 1-h runs; fatigue task 2, three 30-min runs). In fatigue task 1, male ASIC3+/+ mice muscle showed less fatigue than male ASIC3-/- mice and female ASIC3+/+ mice. No differences in fatigue were observed in fatigue task 2. We then tested whether the development of muscle fatigue was dependent on sex and modulated by testosterone. Female ASIC3+/+ mice that were ovariectomized and administered testosterone developed less muscle fatigue than female ASIC3+/+ mice and behaved similarly to male ASIC3+/+ mice. However, testosterone was unable to rescue the muscle fatigue responses in ovariectomized ASIC3-/- mice. Plasma levels of testosterone from male ASIC3-/- mice were significantly lower than in male ASIC3+/+ mice and were similar to female ASIC3+/+ mice. Muscle fiber types, measured by counting ATPase-stained whole muscle sections, were similar in calf muscles from male and female ASIC3+/+ mice. These data suggest that both ASIC3 and testosterone are necessary to protect against muscle fatigue in a task-dependent manner. Also, differences in expression of ASIC3 and the development of exercise-induced fatigue could explain the female predominance in clinical syndromes of pain that include muscle fatigue.


Subject(s)
Muscle Contraction , Muscle Fatigue , Sodium Channels/metabolism , Testosterone/metabolism , Acid Sensing Ion Channels , Animals , Female , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Muscle Fibers, Skeletal/metabolism , Muscle Strength , Muscle, Skeletal/cytology , Muscle, Skeletal/metabolism , Ovariectomy , Pain/metabolism , Physical Exertion , Running , Sex Factors , Sodium Channels/deficiency , Sodium Channels/genetics , Testosterone/administration & dosage , Testosterone/blood
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