Effects of Remimazolam and Propofol on Ca²⁺ Regulation by Ryanodine Receptor 1 with Malignant Hyperthermia Mutation

Figure 2

Representative Ca²⁺ release response of wild-type ryanodine receptor 1- (RYR1-) transfected human embryonic kidney- (HEK-) 293 cells or non-RYR1-transfected HEK-293 cells. Representative traces of agonist-induced Ca²⁺ release by HEK-293 cells transfected with wild-type pcRYR1 cDNA or without any pcRYR1 cDNA. The vertical axis represents the Fura-2 ratio (340/380 nm), i.e., intracellular Ca²⁺ release, and the horizontal axis represents time (minutes). The response of wild-type RYR1 expressing HEK-293 cells to (a) caffeine, (b) caffeine with continuous reflux of remimazolam (546 μM, 100-fold higher than clinical dose), (c) caffeine with continuous reflux of propofol (100 μM, 100-fold higher than the clinical dose), (d) remimazolam (increasing concentrations up to 5020 μM), and (e) propofol (increasing concentrations up to 5000 μM). The response of HEK-293 cells without expressing RYR1 to caffeine (f). No increase in intracellular Ca²⁺ levels for caffeine was observed in HEK-293 cells without expressing RYR1.

(a) Response to caffeine

(b) Response to caffeine under continuous reflux of remimazolam

(c) Response to caffeine under continuous reflux of propofol

(d) Response to remimazolam

(e) Response to propofol

(f) Response of HEK-293 cells without expressing RYR1 to caffeine