Fig. 4: Gentisic acid is a potent Kv7.2/3 and Kv7.3 channel opener.

a Exemplar Kv7.2/3 traces recorded from oocytes in the absence (Control; black) or presence of 50 µM gentisic acid (GA) and 50 µM protocatechuic acid (PA) (red) using the voltage protocol indicated (lower inset). Scale bars center for the pair of traces; n = 8. b Mean peak tail current (left) and normalized tail current (G/Gmax) (right) for traces as in a (measured at arrows shown in a); n = 8, in the absence (black) or presence (red) of compounds indicated. c Mean unclamped oocyte membrane potential for Kv7.2/3-expressing oocytes as in (a); n = 8. d Exemplar Kv7.2/3 traces recorded from oocytes in the absence (Control; black) or presence of 10 nM gentisic acid (GA) (green) using the voltage protocol as in panel (a). Scale bars center for the pair of traces; n = 8 (1 nM, 1 mM), 10 (Control), 9 (all other gentisic acid doses). e Mean peak tail currents for Kv7.2/3 in the absence (black) or presence of the various GA concentrations indicated, using protocol as in (a); n values as in (d). f Mean fold-increase in peak tail current at −60 mV in response to the GA doses as in (e), recorded as in (d), fit with sigmoidal function; n values as in (d). g Dose responses for mean shift in Kv7.2/3 V_0.5act (red) and mean unclamped oocyte membrane potential for Kv7.2/3-expressing oocytes (black) recorded as in (a); n values as in (d). h Exemplar Kv7.2 traces recorded from oocytes in the absence (Control; black) or presence of gentisic acid (GA) (100 µM) (red) (upper) or presence of protocatechuic acid (PA) (100 µM) (red) (lower) using the voltage protocol as in panel (a). Scale bars lower left for the pair of traces; n = 12 (GA); 5 (PA) per group. i Mean peak tail current (left) and normalized tail current (G/Gmax) (right) for traces as in (h) (measured at arrows shown in a); n = 12 (GA); 5 (PA) per group, in the absence (black) or presence (red) of gentisic acid (GA) (100 µM) (upper) or protocatechuic acid (PA) (100 µM) (lower). j Exemplar Kv7.3* traces recorded from oocytes in the absence (Control; black) or presence of 10 nM gentisic acid (GA) (green) using the voltage protocol as in panel (a). Scale bars lower left for the pair of traces; n = 7. k Mean peak tail currents for Kv7.3* in the absence (black) or presence of the various GA concentrations indicated, using protocol as in (a); n = 7 except for the 1 mM group (n = 6). l Mean normalized tail current (G/Gmax) (right) for traces as in j (measured at arrows shown in a); n = 7, in the absence (black) or presence (red) of gentisic acid (GA) (10 nM). Error bars indicate SEM. n indicates number of biologically independent oocytes. Statistical comparisons by t-test. Dashed lines indicate zero current level. Blue boxes contain tail currents for the corresponding traces expanded to preserve scale (test vs control).