Staircase in mammalian muscle without light chain phosphorylation.
In disuse atrophied skeletal muscle, the staircase response is virtually absent and light chain phosphorylation does not occur. The purpose of the present study was to determine if staircase could be restored in atrophied muscle with continued absence of myosin light chain phosphorylation, by reducing what appears to be an otherwise enhanced calcium release. Control (untreated) and sham-operated female Sprague-Dawley rats were compared with animals after 2 weeks of complete inactivity induced by tetrodotoxin (TTX) application to the left sciatic nerve. In situ isometric contractile responses of rat gastrocnemius muscle were analyzed before and after administration of dantrolene sodium (DS), a drug which is known to inhibit Ca2+ release in skeletal 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 and 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 increased 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 with dantrolene permits staircase in atrophied muscle as well as control muscle, by a mechanism which appears to be independent of R-LC phosphorylation.
Rassier
D E
DE
Human Performance Laboratory, University of Calgary, Alberta, Canada.
Tubman
L A
LA
MacIntosh
B R
BR
D000818:Animals; D003620:Dantrolene / Q000627:therapeutic use*; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects*; D009125:Muscle Relaxants, Central / Q000627:therapeutic use*; D018482:Muscle, Skeletal; D009133:Muscular Atrophy / Q000139:chemically induced / Q000188:drug therapy*; D018994:Myosin Light Chains / Q000187:drug effects*; D010766:Phosphorylation; D019946:Propylene Glycol / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin
D009125:Muscle Relaxants, Central; D018994:Myosin Light Chains; D013779:Tetrodotoxin; D019946:Propylene Glycol; D003620:Dantrolene