Modulation of ryanodine-induced contractures in human skeletal muscle pretreated with dantrolene.

Abstract

Dantrolene seems to be the causal therapy in malignant hyperthermia (MH) crisis but the complex mechanisms of MH and dantrolene therapy are still not fully understood. The influence of dantrolene on ryanodine-induced contractures has been reported in animal studies only. In the present study 20 patients from 17 families were tested for MH using the protocol of the European Malignant Hyperthermia Group. In addition ryanodine-induced contractures were evaluated following bolus application of 10.0 mumol.l-1 ryanodine. After pretreatment with 1 mumol.l-1 dantrolene ryanodine-provoked contractures developed significantly later in MHS (15.8 +/- 1.8 min) and MHN (46.0 +/- 4.2 min) muscle specimens than after ryanodine alone (MHS 4.8 +/- 0.7 min. (MHN 13.7 +/- 0.9 min). They were no longer observed in either group after pretreatment with 5 mumol.l-1 dantrolene. We conclude that dantrolene is able to attenuate ryanodine-induced contractures dose-dependently, and therefore it is speculated that dantrolene could specifically act at the ryanodine receptor binding site.