Fig. 7: Expression of Kcnq2 GOF limits repetitive firing of RTN neurons whereas pharmacological inhibition of Kcnq2 favors depolarizing block.
A Segments of membrane potential from RTN neurons in slices from Kcnq2+/+ (black) and Kcnq2 GOF (red) mice during depolarizing current injections (0 to +125pA, 1 s duration) from a membrane potential of −65 mV under control conditions and in the presence of a selective Kcnq2 channel blocker (ML252; 10 µM; Kcnq2+/+ + ML252 = orange; Kcnq2 GOF + ML252 = Cyan). B Input-output relationships (plotted as mean ± SEM) show that under control conditions (top) RTN neurons in slices from Kcnq2 GOF mice (n = 11) generate fewer action potentials in response to depolarizing current injection compared to RTN neurons from control tissue (n = 8) (p = 0.0063; area under curve was compared by unpaired T-test). Note also that bath application of ML252 (10 µM) normalized the response of RTN neurons from each genotype to modest depolarizing current injections (up to 50 pA) but resulted in depolarizing block at more positive steps (B, bottom, p = 0.8162). C Summary data (plotted as mean ± maximum and minimum) show that RTN neurons from Kcnq2 GOF mice (n = 10) have a hyperpolarized resting membrane potential compared to RTN neurons from Kcnq2+/+ mice (n = 9) under control conditions but not in the presence of ML252 (10 µM) (F3,27 = 10.48; p < 0.0001; one-way ANOVA with Tukey’s multiple comparison test). D Summary results (plotted as mean ± maximum and minimum) show that input resistance measured during −100 pA step was similar between genotypes (Kcnq2+/+ n = 9; Kcnq2 GOF n = 8) under control conditions and in the presence of ML252 (10 µM; Kcnq2+/+ + ML252 n = 5; Kcnq2 GOF + ML252 n = 7; one-way ANOVA with Tukey’s multiple comparison test).
