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

Figure 4

Caffeine concentration-dependent Ca²⁺ release in human embryonic kidney (HEK-293) cells transfected with wild-type or mutant ryanodine receptor 1 (RYR1) perfused with remimazolam or propofol. Caffeine-induced Ca²⁺ release in HEK-293 cells transfected with wild-type or mutant RYR1 perfused with remimazolam or propofol. Data were normalized to the maximal response of each cell type. Vertical and horizontal axes represent percentage maximal Ca²⁺ response and caffeine concentration (mM). Data are in cells perfused with or without remimazolam or propofol. Squares and circles represent remimazolam or propofol perfusion and nonperfused groups, respectively. (a–d) Remimazolam and (e–h) propofol perfused cells. Response of (a) wild-type, (b) p.Thr84Met, (c) p.Ser2345Arg, (d) p.Ala4894Thr, (e) wild-type, (f) p.Thr84Met RYR1, (g) p.Ser2345Arg, and (h) p.Ala4894Thr. Curves of all mutant and wild-type RYR1-transfected cells did not show a clear leftward shift under perfusion of remimazolam or propofol.

(a) wild-type: response to caffeine under remimazolam perfusion

(b) p.Thr84Met: response to caffeine under remimazolam perfusion

(c) p.Ser2345Arg: response to caffeine under remimazolam perfusion

(d) p.Ala4894Thr: response to caffeine under remimazolam perfusion

(e) wild-type: response to caffeine under propofol perfusion

(f) p.Thr84Met: response to caffeine under propofol perfusion

(g) p.Ser2345Arg: response to caffeine under propofol perfusion

(h) p.Ala4894Thr: response to caffeine under propofol perfusion