Fig. 4: Carnosic acid potently opens KCNQ3* but not KCNQ2 or KCNQ2/3. | Communications Biology

Fig. 4: Carnosic acid potently opens KCNQ3* but not KCNQ2 or KCNQ2/3.

From: Ancient medicinal plant rosemary contains a highly efficacious and isoform-selective KCNQ potassium channel opener

Fig. 4

a Exemplar plot showing wash-in (red) and partial washout (black) of carnosic acid (5 µM) at −60 mV on KCNQ3* expressed in oocytes. Upper inset, carnosic acid structure. b Mean current fold increase versus [carnosic acid] at −60 mV for KCNQ3*; n = 5 per group. c Mean ΔV0.5act versus [carnosic acid] for oocytes expressing KCNQ3*; n = 5 per group; voltage protocol as in Fig. 3b. d Mean EM versus [carnosic acid] for unclamped oocytes expressing KCNQ3*; n = 5 per group. e Mean traces for KCNQ3* showing effect of carnosic acid (3 µM) (red) on activation. Scale bars lower left; voltage protocol upper inset; n = 5 per group. f Mean activation rate versus voltage for KCNQ3* traces as in f across the voltage range in the absence (black circles) or presence (open red circles) of 3 µM carnosic acid; n = 5 per group. g Mean traces for KCNQ3* showing effect of carnosic acid (3 µM) on deactivation. Scale bars lower left for each trace; voltage protocol upper inset; n = 8 per group. h Mean deactivation rate versus voltage for KCNQ3* traces as in g in the absence (black circles) or presence (open red circles) of 3 µM carnosic acid; n = 8 per group. i Mean traces for KCNQ2 expressed in oocytes in the absence (Control) or presence (blue) of 100 µM carnosic acid. Scale bars lower left; voltage protocol upper inset; n = 5 per group. j Mean traces for KCNQ2/3 expressed in oocytes in the absence (Control) or presence (brown) of 100 µM carnosic acid. Scale bars lower left; voltage protocol upper inset; n = 5 per group. k Mean tail current and normalized tail current (G/Gmax) for KCNQ2 traces as in (I); n = 5 per group. l Mean tail current (left) and normalized tail current (G/Gmax) (right) for KCNQ2/3 traces as in (j); n = 5 per group. m Mean ΔV0.5act versus [carnosic acid] for oocytes expressing KCNQ2 or KCNQ2/3, with KCNQ3* data from panel c for comparison; n = 5 per group; voltage protocol as in (I). n .Mean ΔEM versus [carnosic acid] for oocytes expressing KCNQ2 or KCNQ2/3, with KCNQ3* data (calculated from panel d) for comparison; n = 5 per group; voltage protocol as in panel i. Error bars indicate SEM. n indicates number of biologically independent oocytes.

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