Figure 5.

H₂S triggers a malignant hyperthermia‐susceptible (MHS)‐like response to retigabine in both malignant hyperthermia‐negative (MHN) biopsies and MHN‐derived PHSKMC. (a) Representative trace of skeletal muscle bundle obtained from MHN subjects incubated for 5 min with vehicle (dH₂O) followed by retigabine stimulation (1 mM). No increase in tension was observed. (b) Representative trace of skeletal muscle bundle obtained from MHN subjects incubated for 5 min with NaHS (3 mM) followed by retigabine stimulation (1 mM). The increase in tension achieved was similar to that for MHS samples, that is, >0.2 g above the resting tension. (c) Effect of NaHS (3 mM) or vehicle (dH₂O) incubation in MHN biopsies followed by retigabine stimulation. Values shown are the mean (± SEM; n = 5) increases in tension. *P < .05, significantly different from vehicle. (d) Evaluation of retigabine and XE991, selective K_v7 potassium channel opener and blocker, respectively, on the membrane potential of MHN‐PHSKMC incubated with NaHS. Retigabine exerts a paradoxical depolarizing activity in cells pretreated with NaHS with a similar trend observed in MHS‐derived cells. No difference was detected between the two groups, following XE991. Values shown are the mean (± SEM; n = 5) fluorescence ratios recorded during the experiment. Each experiment was carried out with six replicates. *P < .05, significantly different from vehicle