Calcium Release from Sarcoplasmic Reticulum Is Facilitated in Human Myotubes Derived from Carriers of the Ryanodine Receptor Type 1 Mutations Ile2182Phe and Gly2375Ala
| Autor: | Derk Olthoff, Henrik Rueffert, Markus Wehner, Fritjoff Koenig |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Adult
Male Heterozygote medicine.medical_specialty Muscle Fibers Skeletal chemistry.chemical_element Calcium Ryanodine receptor 2 Cresols Calcium imaging Caffeine Internal medicine medicine Humans Point Mutation Genetic Predisposition to Disease Child Genetics (clinical) Aged Calcium metabolism RYR1 Ryanodine receptor Chemistry Malignant hyperthermia Skeletal muscle Ryanodine Receptor Calcium Release Channel Middle Aged musculoskeletal system medicine.disease Sarcoplasmic Reticulum medicine.anatomical_structure Endocrinology Child Preschool Female Halothane Malignant Hyperthermia tissues Muscle Contraction |
| Zdroj: | Genetic Testing. 7:203-211 |
| ISSN: | 1557-7473 1090-6576 |
| DOI: | 10.1089/109065703322537214 |
| Popis: | Malignant hyperthermia (MH) is caused by increased calcium release from sarcoplasmic reticulum, triggered by volatile anesthetics or depolarizing muscle relaxants. Numerous mutations associated with MH have been detected in the skeletal muscle type ryanodine receptor gene (RyR1), but so far facilitated calcium release has only been demonstrated for a few of them. This is a prerequisite for confirming the causative role of an RyR1 mutation for MH. Calcium release from sarcoplasmic reticulum induced by 4-chloro-m-cresol (4CmC), caffeine, and halothane was determined in human myotubes by calcium imaging. The RyR1 Ile2182Phe mutation and the RyR1 Gly2375Ala mutation have been identified in individuals susceptible to MH. In myotubes of individuals carrying the RyR1 Ile2182Phe or the RyR1 Gly2375Ala mutation, the EC(50) for caffeine and halothane was reduced; in the Ile2182Phe myotubes, the EC(50) for 4CmC was also reduced, all consistent with facilitated calcium release from the sarcoplasmic reticulum. From these data we conclude that both mutations are pathogenic for MH. |
| Databáze: | OpenAIRE |
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