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Enhanced muscle fatigue occurs in male but not female ASIC3-/- mice
Journal article   Open access   Peer reviewed

Enhanced muscle fatigue occurs in male but not female ASIC3-/- mice

Lynn A Burnes, Sandra J Kolker, Jessica F Danielson, Roxanne Y Walder and Kathleen A Sluka
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.294(4), pp.R1347-1355
04/2008
DOI: 10.1152/ajpregu.00687.2007
PMCID: PMC2746663
PMID: 18305024
url
https://doi.org/10.1152/ajpregu.00687.2007View
Published (Version of record) Open Access

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

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