title: 4-Chloro-m-cresol: a specific tool to distinguish between malignant hyperthermia-susceptible and normal muscle.
abstract: Single-channel recordings have indicated that ryanodine receptor (RyR1) mutation Arg615Cys of porcine malignant hyperthermia-susceptible (MHS) muscle is not directly associated with the enhanced caffeine sensitivity of MH(S) muscle [1]. In the present study, the effect of a novel activator of RyR1, 4-chlorom-cresol (4-CmC), was investigated on high-affinity [3H]ryanodine binding to porcine skeletal sarcoplasmic reticulum. The 4-CmC affinity of [3H]ryanodine binding to MHS vesicles was 2-fold higher compared to that in normal tissue. This enhanced affinity was confirmed when the effect of 4-CmC on [3H]ryanodine binding to the isolated CHAPS-solubilized MHS RyR1 was investigated. 4-CmC is, therefore, suggested to be a potent tool to distinguish between Ca2+ release from MHS and normal muscle.
authors.affiliation: Department of Applied Physiology, University of Ulm, Germany. annegret.herrmann-frank@medizin.uni-ulm.de
authors.forename: A
authors.initials: A
authors.lastname: Herrmann-Frank
authors.forename: M
authors.initials: M
authors.lastname: Richter
authors.forename: F
authors.initials: F
authors.lastname: Lehmann-Horn
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003408:Cresols / Q000494:pharmacology*; D008305:Malignant Hyperthermia / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D012433:Ryanodine / Q000378:metabolism*; D013552:Swine; D014316:Tritium
chemical_list: D003408:Cresols; D014316:Tritium; D012433:Ryanodine; C006984:chlorocresol; D002110:Caffeine; D002118:Calcium