Fig. 5. Loss of Kvβ2 catalytic function prevents redox-mediated increases in Kv1 activity and vasodilation, and suppresses MBF.

A Schematic illustration depicting abolished NADPH-dependent carbonyl reduction by Kvβ2 resulting from the Y90F point mutation. B Single-channel recordings showing Kv1 activity in membrane patches from Kvβ2^Y90F mice before and after application of 1 mM NADH. C Summary of Kv1 open probabilities (nPo; mean values ± SEM) in membrane patches from Kvβ2^Y90F mice before and after application of 1 mM NADH. n = 7 cells from 3 mice; ns: P ≥ 0.05 (two-sided Wilcoxon matched-pairs signed rank test). D Representative arterial diameter recordings in arteries from wild type (129SvEv) and Kvβ2^Y90F mice in the absence and presence of l-lactate (5–20 mM) in the perfusate (i.); and, summary of percent change in diameter (mean values ± SEM) in response to l-lactate (5–20 mM) relative to baseline (⎯ l-lactate, ii.). wt: n = 5 arteries from 4 mice, Kvβ2^Y90F: n = 6 arteries from 5 mice. ***p = 0.00001 (two-way repeated measures ANOVA). E Representative arterial diameter recordings in arteries from wild type (129SvEv) and Kvβ2^Y90F mice in the absence and presence of H₂O₂ (0.1–10 μM) in the perfusate (i.); and, summary of percent change in diameter (mean values ± SEM) in response to H₂O₂ (0.1–10 μM) relative to baseline (⎯ Η₂Ο₂, ii.). wt: n = 4 arteries from 4 mice, Kvβ2^Y90F: n = 4 arteries from 3 mice. ***p = 0.0004 (two-way repeated measures ANOVA). F Summary (mean values ± SEM) of mean arterial pressure (MAP) and heart rate (HR) in wild type and Kvβ2^Y90F mice during intravenous norepinephrine infusion (0–5 μg/kg/min). n = 9–15 mice, ns: P ≥ 0.05 (two-way repeated measures ANOVA). G Summary (mean values ± SEM) of relationships between MBF (ml/min/g) cardiac work (pressure rate product; bpm × mmHg) in wild type (wt; 129SvEv) versus Kvβ2^Y90Fmice. **p = 0.0043, slope wt vs. Kvβ2^Y90F, n = 4–6 mice, (linear regression). Source data are provided as a Source Data file.