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- Title
Propofol-induced changes in myoplasmic calcium concentrations in cultured human skeletal muscles from RYR1 mutation carriers.
- Authors
Migita, T.; Mukaida, K.; Kawamoto, M.; Kobayashi, M.; Nishino, I.; Yuge, O.; Yuget, O
- Abstract
Malignant hyperthermia is a pharmacogenetic disorder caused by autosomal dominant mutations in the ryanodine receptor type 1 gene. Propofol has been reported as a safe anaesthetic for malignant hyperthermia susceptible patients but has not been tested on cultured cells from patients with the ryanodine receptor type 1 mutation. The aim of this study was to determine whether propofol could trigger abnormal calcium fluxes in human myotubes isolated from malignant hyperthermia susceptible patients harbouring the native ryanodine receptor type 1 mutation. Muscle specimens were obtained from the patients to diagnose malignant hyperthermia disposition and the calcium-induced calcium release test and molecular genetic analyses were performed. Using the calcium sensitive probe Fura 2, we determined the 340/380 nm wave-length ratios by measuring alterations in calcium homeostasis in isolated myotubes from cultured skeletal muscle specimens. Two patients, one with ryanodine receptor type 1 R2508C and one with the L4838V mutation had accelerated calcium-induced calcium release rates. The 340/380 nm ratios increased when the propofol concentration exceeded 100 microM. The half-maximal activation concentrations (EC50) for propofol from patients 1 and 2 were 181.1 and 420.5 microM, respectively. Increases in calcium concentrations in response to propofol dosage were limited to doses at least 100-fold greater than those used in clinical settings. These observations correlate well with clinical observations that propofol does not trigger malignant hyperthermia in susceptible humans.
- Subjects
CALCIUM metabolism; CALCIUM; CELL culture; COMPARATIVE studies; INTRAVENOUS anesthetics; MALIGNANT hyperthermia; RESEARCH methodology; MEDICAL cooperation; MOLECULAR biology; GENETIC mutation; RESEARCH; EVALUATION research; PROPOFOL; SKELETAL muscle; PHARMACODYNAMICS
- Publication
Anaesthesia & Intensive Care, 2007, Vol 35, Issue 6, p894
- ISSN
0310-057X
- Publication type
journal article