Staircase in mammalian muscle without light chain phosphorylation

In disuse atrophied skeletal muscle, the staircase response is virtually ab sent and light chain phosphorylation does not occur. The purpose of the pre sent study was to determine if staircase could be restored in atrophied mus cle with continued absence of myosin Light chain phosphorylation, by reduci ng what appears to be an otherwise enhanced calcium release. Control (untre ated) and sham-operated female Sprague-Dawley rats were compared with anima ls after 2 weeks of complete inactivity induced by tetrodotoxin (TTX) appli cation to the left sciatic nerve. In situ isometric contractile responses o f rat gastrocnemius muscle were analyzed before and after administration of dantrolene sodium (DS), a drug which is known to inhibit Ca2+ release in s keletal muscle. Twitch active force (AF) was attenuated by DS from 2.2 +/- 0.2 N, 2.7 +/- 0.1 N and 2.4 +/- 0.2 N to 0.77 +/- 0.2 N, 1.05 +/- 0.1 N an d 1.01 +/- 0.2 N in TTX (N = 5), sham (N = 11) and control (N = 7) muscles, respectively. Following dantrolene treatment, 10 s of 10-Hz stimulation in creased AF to 1.32 +/- 0.2 N, 1.52 +/- 0.1 N and 1.45 +/- 0.2 N for the TTX , sham and control groups, respectively, demonstrating a positive staircase response. Regulatory light chain (R-LC) phosphorylation was lower for TTX- treated (5.5 +/- 5.5%) than for control (26.1 +/- 5.3%) and sham (20.0 +/- 5%) groups. There was no significant change from resting levels for any of the groups after DS treatment (P = 0.88). This study shows that treatment w ith dantrolene permits staircase in atrophied muscle as well as control mus cle, by a mechanism which appears to be independent of R-LC phosphorylation .