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Received December 27, 2005
Revised January 27, 2006
Accepted after revision January 31, 2006
1 Karolinska Institutet
* To whom correspondence should be addressed. E-mail: hakan.westerblad{at}ki.se.
Isolated whole skeletal muscles fatigue more rapidly than isolated single muscle fibres. We have now employed this difference to study mechanisms of skeletal muscle fatigue. Isolated whole soleus and EDL muscles were fatigued by repeated tetanic stimulation while measuring force production. Neither application of 10 mM lactic acid nor increasing the [K+] of the bath solution from 5 to 10 mM had any significant effect on the rate of force decline during fatigue induced by repeated brief tetani, while soleus muscles fatigued slightly faster during continuous tetanic stimulation. Inhibition of mitochondrial respiration with cyanide resulted in a faster fatigue development in both soleus and EDL muscles. Single soleus muscle fibres were fatigued by repeated tetani while measuring force and myoplasmic free [Ca2+] ([Ca2+]i). Under control conditions, the single fibres were substantially more fatigue resistant than the whole soleus muscles; tetanic force at the end of a series of 100 tetani was reduced by about 10 and 50%, respectively. However, in the presence of cyanide, fatigue developed at a similar rate in whole muscles and single fibres and tetanic force at the end of fatiguing stimulation was reduced by ~80%. The force decrease in the presence of cyanide was associated with a ~50% decrease in tetanic [Ca2+]i, compared with an increase of ~20% without cyanide. In conclusion, lactic acid or [K+] has little impact on fatigue induced by repeated tetani, whereas hypoxia speeds up fatigue development and this is mainly due to an impaired Ca2+ release from the sarcoplasmic reticulum.
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