The goal of this study was to determine the roles of metabolic and non
metabolic factors in muscle fatigue. Rat gastrocnemius muscles were fa
tigued by stimulation of the nerve (n = 6) or muscle (n = 4, after 2 d
ays of denervation). (31)Phosphorus nuclear magnetic resonance spectro
scopy was used to measure levels of intracellular inorganic phosphate
(Pi) and hydrogen ions (H+) (which are thought to inhibit contraction)
and the high-energy phosphates, phosphocreatine (PCr), and ATP. For b
oth indirect and direct stimulation, with fatigue to approximate to 60
% initial tetanic force, [Pi] increased from approximate to 3.5 mmol/L
to approximate to 20 mmol/L and [PCr] decreased from approximate to 2
7 mmol/L to approximate to 9 mmol/L. However, with continued fatigue t
o 25-35% initial tetanic force, neither [Pi] or [PCr] changed further.
[ATP] and pH changed only slightly during fatigue. The results are co
nsistent with early fatigue arising from metabolic inhibition of contr
action; but later fatigue arising independent of metabolites, due to i
mpaired activation beyond the neuromuscular junction. (C) 1994 John Wi
ley & Sons, Inc.