Fig. 2: LAKI specifically photoblocks TREK1, TREK2 and TRESK in native small sensory neurons.

a Whole-cell current recordings elicited at different holding potentials from wild-type (WT) TG neurons in the presence of LAKI (10 µM) upon alternating illumination at 480 nm (blue) and 365 nm (magenta). b IV relationship of the photocurrent density induced by alternating illumination (I_480 nm – I_365 nm) in WT TG neurons in the presence of LAKI (10 µM). n was obtained from six mice from two independent experiments. c Whole-cell current recordings elicited at 0 mV from WT TG neurons, Trek1^−/−/Trek2^−/− TG neurons and Trek1^−/−/Trek2^−/− TG neurons overexpressing TRESK-MT1 in the presence of LAKI (10 µM) upon alternating illumination at 480 nm (blue) and 365 nm (magenta). d IV relationship of the photocurrent density (I_{480 nm} – I_{365 nm}) in WT TG neurons, Trek1^−/−/Trek2^−/− TG neurons and Trek1^−/−/Trek2^−/− TG neurons overexpressing TRESK-MT1 in presence of LAKI (10 µM). Statistical significance was determined by a mixed-effects model with repeated measures followed by Holm–Sidak’s post-test (***p < 0.001 compared WT TG with Trek1^−/−/Trek2^−/− TG and Trek1^−/−/Trek2^−/− TG + TRESK-MT1; ###p < 0.001, #p < 0.05 compared Trek1^−/−/Trek2^−/− TG with Trek1^−/−/Trek2^−/− TG⁺ TRESK-MT1). The number of tested neurons is for WT n = 10 at −80 mV, n = 9 at −60 mV, n = 11 at −40, −20, and 0 mV from six mice from two independent experiments; for Trek1^-/-/Trek2^-/- n = 7 at −80 and −60 mV, n = 9 at −40, −20, and 0 mV from six mice from two independent experiments; for Trek1^−/−/Trek2^−/− + TRESK-MT1 n = 8 at −80, −60, −40, −20, and 0 mV from six mice from two independent experiments. e Representative voltage trace showing the firing modulation of WT TG neurons in the presence of LAKI (10 µM) upon alternating illumination at 480 nm (blue) and 365 nm (magenta). f Graph summarizing the average firing rate of WT TG neurons. n was obtained from 6 mice from two independent experiments. Statistical significance was determined by a two-sided paired t-test (**p = 0.0053). Data were represented as mean ± SEM. The numbers of tested neurons are indicated in parentheses on the graph.