To assess the impairment of muscle membrane excitation, excitation-con
traction (E-C) coupling, and contractility during muscle fatigue, we m
onitored the contracture responses of resting and fatigued muscles on
exposure to high potassium and caffeine. On exposure to 140 mmol/L pot
assium, mouse extensor digitorum longus (EDL) developed a contracture
which was 15.7% of tetanic tension before fatigue and 31.7% after fati
gue, while soleus developed 59.4% contracture before and 68.8% after f
atigue. Potassium causes contractures by depolarizing the muscle fiber
membrane. Hence, membrane excitation is reduced in fatigued EDL and s
oleus. On exposure to 32 mmol/L caffeine, the contracture was 7.1% in
resting EDL, 8.5% in fatigued EDL, 50.1% in resting soleus, and 43.7%
in fatigued soleus. On exposure to 1 mmol/L caffeine followed by rapid
cooling, the contracture was 3.0% in resting EDL, 3.2% in fatigued ED
L, 21.5% in resting soleus, and 10.3% in fatigued soleus. Caffeine cau
ses contracture by releasing Ca++ from the sarcoplasmic reticulum. Our
results indicate reduced E-C coupling attributable to reduced membran
e excitation in fatigued EDL, and reduced contractility in fatigued so
leus. (C) 1994 John Wiley & Sons, Inc.