ROLE OF EXTRACELLULAR [CA2-MUSCLE(] IN FATIGUE OF ISOLATED MAMMALIAN SKELETAL)

The possible role of altered extracellular Ca2+ concentration ([Ca2+]( o)) in skeletal muscle fatigue was tested on isolated slow-twitch sole us 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 soluti ons, had little effect on tetanic force in nonfatigued muscle. 2) Almo st complete restoration of tetanic force was induced by 10 mM [Ca2+](o ) in severely Ki-depressed muscle (extracellular Kf concentration of 1 0-12 mM). This effect was attributed to a 5-mV reversal of the K+-indu ced depolarization and subsequent restoration of ability to generate a ction potentials (inferred by using the twitch force-stimulation stren gth 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 re versed 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 e xacerbated at low [Ca2+](o). These combined results suggest, first, th at raised [Ca2+](o) protects against fatigue rather than inducing it a nd, second, that a considerable depletion of [Ca2+](o) in the transver se tubules may contribute to fatigue.