Staircase, fatigue, and caffeine in skeletal muscle in situ.

The specific locus of impairment in excitation-contraction coupling that is associated with skeletal muscle fatigue has not been identified. In the present study the phenomena of staircase and fatigue were studied in the rat gastrocnemius muscle in situ, and the effect of caffeine (50 mg kg-1) given prior to or during 5 minutes of stimulation was observed. A 10 Hz indirect stimulation resulted in a staircase response that proceeded for 10.4 +/- 1.6 (mean +/- SD) seconds, reaching a peak force value that was 70-75% higher than the initial contraction. After 5 minutes of stimulation and 20 minutes of rest, the staircase response was longer (17 +/- 3.1 seconds) and proceeded more slowly when the stimulation regimen was repeated. Caffeine accelerated the fatigue and reversed the effect of fatigue on the staircase response. Since caffeine enhances the release of Ca2+ from terminal cisternae, it is postulated that the accelerated fatigue in the presence of caffeine is indicative of a reduced availability of Ca2+ for release. This hypothesis would also explain the slower progression of staircase in the fatigued muscle.