Figure 3.
Activation of Kv7 channels induces a paradoxical depolarizing (DEP) response in primary human skeletal muscle cells (PHSKMC) derived from malignant hyperthermia‐susceptible (MHS) biopsies (susceptible subjects). (a) Evaluation of activators and blockers of KATP, BKCa, and Kv7 channels on the membrane potential of malignant hyperthermia‐negative (MHN)‐derived PHSKMC. As expected, the K channel activators evoked a hyperpolarizing (HYP) effect, while the K channel blockers induced a DEP effect. (b) Evaluation of activators and blockers of KATP, BKCa, and Kv7 potassium channels on the membrane potential of MHS‐derived PHSKMC reveals a significant reversal of the response to the Kv7 channel opener, retigabine, compared with that observed in PHSKMC from MHN patients. Values shown are the mean (± SEM; n = 5) fluorescence ratios recorded for HYP or DEP compounds during the experiment. Each experiment was carried out with six replicates. The asterisks indicate a significant depolarizing difference from the effect evoked by vehicle (*P < .05). The symbol § indicates a significant hyperpolarizing difference from the effect evoked by vehicle (§ P < .05).