Fatigue and metabolism of frog muscle fibers during stimulation and in response to caffeine.

Tension and metabolite concentrations were measured in single frog muscle fibers at 15 degrees C in vitro, in response to electrical stimulation or to immersion in caffeine- or potassium chloride-Ringer. Sarcomere length equaled 2.3 micrometers. Interrupted stimulation for 150 s at 20 Hz or stimulation for 7.5 min at 1 Hz was followed by at least 20 min of fatigue, evidenced by a reduced 200-ms test contraction. Fatigued fibers contracted maximally in potassium chloride- or caffeine-Ringer. They had high lactate and glucose 6-phosphate concentrations and a reduced phosphocreatine (PCr) concentration. Adenosine 5'-triphosphate (ATP) concentration was approximately normal but was markedly reduced by a caffeine contracture. A plot of PCr consumption against the tension-time integral at different stimulation frequencies (25, 35, or 50 Hz) and durations had an intercept of 25.5 nmol PCr/mg protein at time zero and a corrected slope of 0.65 nmol approximately P/mg protein per kg . s . cm-2. Prolonged fatigue is not due to energy exhaustion or to the inability of muscle fibers to consume residual ATP but probably arises from long-lasting interference in excitation-contraction coupling, which can be reversed by KCl- or caffeine-induced release of Ca2+ from intracellular stores.