Skeletal muscle staircase response with fatigue or dantrolene sodium

It has been postulated that the staircase response of skeletal muscle is effected by Ca2+-dependent phosphorylation of myosin light chains. Dantrolene inhibits calcium release from the sarcoplasmic reticulum, so treatment with dantrolene should prolong the time required to reach the peak of the staircase response. Furthermore, since it has been postulated that Ca2+ release is attenuated by fatigue, there should be similarities between the staircase of fatigued muscle and staircase in the presence of dantrolene. The left gastrocnemius muscle of anesthetized rats was isolated in situ and connected to an isometric transducer. In the control condition, developed tension increased for approximately 10 s with repetitive stimulation at 10 Hz. The time to reach the peak of staircase was prolonged after a 5 min period of stimulation at 10 Hz or after injection of dantrolene sodium (0.8 mg.kg-1 IV). Other similarities between the dantrolene treated group and the fatigue group include the following: contraction time was shorter in fatigue (12.8 +/- 0.8 ms) and with dantrolene (14.7 +/- 1.3 ms) than in the controls (16.4 +/- 1 ms), and half-relaxation time increased from 5 s (10.8 +/- 9 ms) to 15 s (13.8 +/- 0.8 ms) of staircase in the control but did not increase at this time in the dantrolene or fatigue groups. This study demonstrates that both fatigue and a reduction in Ca2+ release from sarcoplasmic reticulum will prolong the time required to reach the peak of staircase.