Heteromeric complexes of aldo-keto reductase auxiliary K V β subunits (AKR6A) regulate sarcolemmal localization of K V 1.5 in coronary arterial myocytes.

Redox-sensitive potassium channels consisting of the voltage-gated K+ (KV ) channel pore subunit KV 1.5 regulate resting membrane potential and thereby contractility of vascular smooth muscle cells. Members of the KV 1 family associate with cytosolic auxiliary β subunits, which are members of the aldo-keto reductase (AKR) superfamily (AKR6A subfamily). The Kvβ subunits have been proposed to regulate Kv1 gating via pyridine nucleotide cofactor binding. However, the molecular identity of KV β subunits that associate with native KV 1.5 channels in the vasculature is unknown. Here, we examined mRNA and protein expression of KV β subunits and tested whether KV β isoforms interact with KV 1.5 channels in murine coronary arteries. We detected KV β1 (AKR6A3), KV β2 (AKR6A5) and KV β3 (AKR6A9) transcripts and KV β1 and KV β2 protein in left anterior descending coronary arteries by real time quantitative PCR and Western blot, respectively. In situ proximity ligation assays indicated abundant protein-protein interactions between KV 1.5/KV β1, KV 1.5/KV β2 and KV β1/β2 in coronary arterial myocytes. Confocal microscopy and membrane fractionation analyses suggest that arterial myocytes from KV β2-null mice have reduced abundance of sarcolemmal KV 1.5. Together, data suggest that in coronary arterial myocytes, KV 1.5 channels predominantly associate with KV β1 and KV β2 proteins and that KV β2 performs a chaperone function for KV 1.5 channels in arterial myocytes, thereby facilitating Kv1α trafficking and membrane localization.