Dantrolene, like fatigue, has a length-dependent effect on submaximal force-length relationships of rat gastrocnemius muscle.

AIM: Fatigue is length-dependent; relative active force depression is greater when measured at short lengths than at long lengths. Several unsatisfactory mechanisms have been proposed to explain this length dependence of fatigue, including: damaged myofilaments, stretch of 'in-series' structures, impaired t-tubule conduction and reduced intensity of activation. Dantrolene targets the ryanodine receptors, inhibiting stimulation-induced release of Ca2+. The purpose of this study was to determine if the force depression caused by dantrolene treatment also has a length dependence.

METHODS: Submaximal (single-pulse, double-pulse and 50 Hz stimulation) active force-length relationships were obtained from the medial gastrocnemius muscle of anaesthetized rats, before and after intravenous injection with dantrolene dissolved in propylene glycol.

RESULTS: Dantrolene treatment was sufficient to reduce twitch amplitude by 25%. Similar to the consequences of repetitive stimulation, dantrolene treatment caused the same decrease in absolute active force across a broad range of test lengths, for twitch, double-pulse and 50 Hz contractions. Considering that active force is smaller at short lengths than at long lengths, this similar absolute force decrease represents a greater relative decrease at short lengths. Clearly, there is a length-dependent impact of attenuated Ca2+ release by dantrolene on relative active force.

CONCLUSION: This study demonstrates that there is a length dependence of force depression associated with decreased Ca2+ release due to dantrolene treatment; therefore, if fatigue is due to decreased Ca2+ release, then additional length-dependent mechanisms are not required to explain the reported length dependence of force depression.