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J Appl Physiol 84: 1395-1406, 1998;
8750-7587/98 $5.00
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Vol. 84, Issue 4, 1395-1406, April 1998

Role of extracellular [Ca2+] in fatigue of isolated mammalian skeletal muscle

Simeon P. Cairns1,2, Wayne A. Hing1,3, John R. Slack1, Roland G. Mills4, and Denis S. Loiselle1

1 Department of Physiology, School of Medicine, University of Auckland, Auckland; 2 Kinesiology Group, School of Physical Education, University of Otago, Dunedin; 3 Auckland School of Physiotherapy, Auckland Institute of Technology, Auckland; and 4 Department of Physiology, School of Medicine, University of Otago, Dunedin, New Zealand

The possible role of altered extracellular Ca2+ concentration ([Ca2+]o) in skeletal muscle fatigue was tested on isolated slow-twitch soleus and fast-twitch extensor digitorum longus muscles of the mouse. The following findings were made. 1) A change from the control solution (1.3 mM [Ca2+]o) to 10 mM [Ca2+]o, or to nominally Ca2+-free solutions, had little effect on tetanic force in nonfatigued muscle. 2) Almost complete restoration of tetanic force was induced by 10 mM [Ca2+]o in severely K+-depressed muscle (extracellular K+ concentration of 10-12 mM). This effect was attributed to a 5-mV reversal of the K+-induced depolarization and subsequent restoration of ability to generate action potentials (inferred by using the twitch force-stimulation strength relationship). 3) Tetanic force depressed by lowered extracellular Na+ concentration (40 mM) was further reduced with 10 mM [Ca2+]o. 4) Tetanic force loss at elevated extracellular K+ concentration (8 mM) and lowered extracellular Na+ concentration (100 mM) was partially reversed with 10 mM [Ca2+]o or markedly exacerbated with low [Ca2+]o. 5) Fatigue induced by using repeated tetani in soleus was attenuated at 10 mM [Ca2+]o (due to increased resting and evoked forces) and exacerbated at low [Ca2+]o. These combined results suggest, first, that raised [Ca2+]o protects against fatigue rather than inducing it and, second, that a considerable depletion of [Ca2+]o in the transverse tubules may contribute to fatigue.

potassium; calcium concentration; excitability; skeletal muscle contraction


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