Effect of SMB-1 on K_V7.2-W236L.

<p>(<b>A</b>) Representative current traces for K_V7.2-W236L in the absence and presence of 10 µM SMB-1 (<b>B</b>) Effect of SMB-1 on current-voltage relationship. (<b>C</b>) Effect of SMB-1 on voltage-dependence of activation. (<b>D</b>) Effect of SMB-1 on deactivation kinetics. Statistical significance was determined by paired, two-tailed Student's <i>t</i>-test. Representative tail current traces in the absence and presence of 10 µM SMB-1 are shown in the inset. Effect of SMB-1 on the fast (<b>E</b>) and slow (<b>F</b>) component of the activation kinetics. Statistical significance was determined by two-way repeated measurements ANOVA followed by Bonferroni post-test. Y-values were log-transformed before the statistical analysis to meet the assumption of normality. * <i>p<</i>0.05, ** <i>p<</i>0.01, *** <i>p<</i>0.001. Bars represent S.E.M and <i>n = </i>4–6.</p

Effect of SMB-1 on channels with mutations in the refined retigabine binding site.

<p>Effect of 10 µM SMB-1 on the current-voltage relationship of (A) K_V7.2-L275V, (B) K_V7.2-L299V and (C) K_V7.4-L305V. Bars represent S.E.M. and <i>n = </i>4–6.</p

Inhibition of K_V7.2 by SMB-1.

<p>Chemical structure of (S)-2 (<b>A</b>) and SMB-1 (<b>B</b>). (<b>C</b>) Representative current traces for K_V7.2 in the absence and presence of 10 µM SMB-1 (<b>D</b>) Effect of SMB-1 on current-voltage relationship. (<b>E</b>) Effect of SMB-1 on voltage-dependence of activation. (<b>F</b>) Effect of SMB-1 on deactivation kinetics. Statistical significance was determined by paired, two-tailed Student's <i>t</i>-test. Representative tail current traces in the absence and presence of 10 µM SMB-1 are shown in the inset. Effect of SMB-1 on the fast (<b>G</b>) and slow (<b>H</b>) component of the activation kinetics. Statistical significance was determined by two-way repeated measurements ANOVA followed by Bonferroni post-test. Y-values were log-transformed before the statistical analysis to meet the assumption of normality. (<b>I</b>) Dose-response relationship for the effect of SMB-1 on K_V7.2. *** <i>p<</i>0.001. Bars represent S.E.M and <i>n = </i>5–9. Note that the error bars in some instances are too small to be visible.</p

Plasma and brain exposure of SMB-1 in rats following subcutaneous administration of 20 mg/kg.

<p>Data shown as mean total concentrations ± S.E.M (n = 3).</p

Activation of K_V7.4 by SMB-1.

<p>(<b>A</b>) Representative current traces for K_V7.4 in the absence and presence of 10 µM SMB-1. (<b>B</b>) Effect of SMB-1 on current-voltage relationship. (<b>C</b>) Effect of SMB-1 on voltage-dependence of activation. (<b>D</b>) Effect of SMB-1 on deactivation kinetics. Statistical significance was determined by paired, two-tailed Student's <i>t</i>-test. Representative tail current traces in the absence and presence of 10 µM SMB-1 are shown in the inset. (<b>E</b>) Effect of SMB-1 on activation kinetics. Statistical significance was determined by two-way repeated measurements ANOVA followed by Bonferroni post-test. (<b>F</b>) Dose-response relationship of SMB-1 on K_V7.4. *** <i>p<</i>0.001. Bars represent S.E.M and <i>n = </i>5–8.</p

Effect of SMB-1 on K_V7.4-W242L.

<p>(<b>A</b>) Representative current traces for K_V7.4-W242L in the absence and presence of 10 µM SMB-1. (<b>B</b>) Effect of SMB-1 on current-voltage relationship. (<b>C</b>) Effect of SMB-1 on voltage-dependence of activation. (<b>D</b>) Effect of SMB-1 on deactivation kinetics. Statistical significance was determined by paired, two-tailed Student's <i>t</i>-test. Representative tail current traces in the absence and presence of 10 µM SMB-1 are shown in the inset (note that the traces are completely overlapping). (<b>E</b>) Effect of SMB-1 on activation kinetics. Statistical significance was determined by two-way repeated measurements ANOVA followed by Bonferroni post-test. Bars represent S.E.M and <i>n = </i>5.</p