title: 3,4-Methylenedioxymethamphetamine (Ecstasy) increases the sensitivity of the contractile apparatus to calcium ions in both malignant hyperthermia-susceptible and normal skeletal muscle fibres.
abstract: OBJECTIVE
  The present study was designed to investigate whether 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') increases the sensitivity of the contractile apparatus to calcium in muscle fibres from malignant hyperthermia-susceptible and malignant hyperthermia-negative pigs, whether it causes calcium ion release from the sarcoplasmic reticulum and whether it inhibits calcium reuptake into the sarcoplasmic reticulum.
  
  
  METHODS
  Experimental study, using a model of porcine saponin-skinned fibres.
  
  
  RESULTS
  Administration of MDMA in concentrations of 1, 2 and 4 mmol l(-1)l did not result in relevant force transients in skinned muscle fibres of malignant hyperthermia-susceptible or malignant hyperthermia-negative pigs. Furthermore, MDMA in these concentrations did not alter calcium ion loading of the sarcoplasmic reticulum in either group. With regard to changes in the calcium ion sensitivity of the contractile proteins, however, MDMA dose-dependently increased (pCa50) values (negative decadic logarithm of [Ca2+] at which isometric force is half-maximal) in both groups.
  
  
  CONCLUSIONS
  In the present study, we were able to demonstrate that MDMA dose-dependently increases the sensitivity of the contractile apparatus to calcium in both malignant hyperthermia-susceptible and malignant hyperthermia-negative fibres. Consequently, the malignant hyperthermia status should not affect the calcium sensitivity of the contractile apparatus. However, the increased calcium sensitivity is an important finding that must be appreciated, particularly in relation to the agonistic effect of MDMA at the nicotinic acetylcholine receptor, which increases intracellular calcium ion concentrations.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Hospital Cologne Merheim, University of Witten-Herdecke, Cologne, Germany. mark.gerbershagen@uni-wh.de
authors.forename: Mark U
authors.initials: MU
authors.lastname: Gerbershagen
authors.forename: Goetz
authors.initials: G
authors.lastname: Missler
authors.forename: Jan K
authors.initials: JK
authors.lastname: Schütte
authors.forename: Alexander
authors.initials: A
authors.lastname: Starosse
authors.forename: Bernhard M
authors.initials: BM
authors.lastname: Graf
authors.forename: Frank
authors.initials: F
authors.lastname: Wappler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Zink
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008305:Malignant Hyperthermia / Q000235:genetics / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D053580:Muscle Strength / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013552:Swine
chemical_list: D018817:N-Methyl-3,4-methylenedioxyamphetamine