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Effects of Remimazolam and Propofol on Ca 2+ Regulation by Ryanodine Receptor 1 with Malignant Hyperthermia Mutation.

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  • معلومة اضافية
    • المصدر:
      Publisher: Wiley Country of Publication: United States NLM ID: 101600173 Publication Model: eCollection Cited Medium: Internet ISSN: 2314-6141 (Electronic) NLM ISO Abbreviation: Biomed Res Int Subsets: MEDLINE
    • بيانات النشر:
      Publication: 2024- : [Hoboken, NJ] : Wiley
      Original Publication: New York, NY : Hindawi Pub. Co.
    • الموضوع:
      Ryanodine Receptor Calcium Release Channel*/genetics ; Ryanodine Receptor Calcium Release Channel*/metabolism; Benzodiazepines/*pharmacology ; Calcium/*metabolism ; Malignant Hyperthermia/*genetics ; Propofol/*pharmacology; Anesthetics/pharmacology ; Caffeine/metabolism ; HEK293 Cells ; Humans ; Mutation/genetics
    • نبذة مختصرة :
      Background: We investigated the potential safety of remimazolam and propofol in malignant hyperthermia- (HM-) susceptible patients using ryanodine receptor 1- (RYR1-) expressing human embryonic kidney- (HEK-) 293 cells.
      Methods: We compared the enhanced responsiveness of HEK-293 cells expressing wild-type RYR1 with that of mutant RYR1 to caffeine following perfusion with remimazolam or propofol. Furthermore, we investigated whether RYR1 enhanced the responsiveness of cells to remimazolam or propofol and compared the median effective concentration (EC 50 ; i.e., the concentration required to reach half-maximal activation) using an unpaired two-tailed t -test while a P < 0.05 was considered significant.
      Results: Remimazolam and propofol did not promote the caffeine-induced increase in intracellular Ca 2+ levels in HEK-293 cells expressing mutant RYR1 even with exposure to approximately 100-fold the clinically used concentration. In wild-type RYR1, EC 50 values of remimazolam following refusion vs. nonperfusion were 2.86 mM vs. 2.75 mM ( P = 0.76) while for propofol perfusion vs. nonperfusion, they were 2.76 mM vs. 2.75 mM, respectively ( P = 0.83). In mutant RYR1, EC 50 values of remimazolam refusion vs. nonperfusion were 1.58 mM vs. 1.71 mM, respectively ( P = 0.63) while for propofol perfusion vs. nonperfusion, they were 1.65 mM vs. 1.71 mM, respectively ( P = 0.73). Remimazolam and propofol increased intracellular Ca 2+ levels in a concentration-dependent manner, but the effect was not enhanced by RYR1. EC 50 values of remimazolam with non-RYR1 vs. wild-type RYR1 were 1.00 mM vs. 0.92 mM, respectively ( P = 0.91) while those of propofol were 1.09 mM vs. 1.05 mM, respectively ( P = 0.84).
      Conclusions: The increase in intracellular Ca 2+ concentration caused by remimazolam or propofol was not considered an RYR1-mediated reaction. We conclude that remimazolam and propofol can be safely used as an anesthetic in MH-susceptible patients with RYR1 -mutation without causing MH and may be safely substituted for an MH-triggering anesthetic when RYR1-mediated MH occurs.
      Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article.
      (Copyright © 2021 Tomoyuki Watanabe et al.)
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    • الرقم المعرف:
      0 (Anesthetics)
      0 (RYR1 protein, human)
      0 (Ryanodine Receptor Calcium Release Channel)
      12794-10-4 (Benzodiazepines)
      3G6A5W338E (Caffeine)
      7V4A8U16MB (remimazolam)
      SY7Q814VUP (Calcium)
      YI7VU623SF (Propofol)
    • الموضوع:
      Date Created: 20210125 Date Completed: 20210528 Latest Revision: 20240330
    • الموضوع:
      20250114
    • الرقم المعرف:
      PMC7801102
    • الرقم المعرف:
      10.1155/2021/8845129
    • الرقم المعرف:
      33490280