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

Abstract

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. 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. 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. 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.