Heteromeric KV2/KV8.2 Channels Mediate Delayed Rectifier Potassium Currents in Primate Photoreceptors

Silent voltage-gated potassium channel subunits (KVS) interact selectively with members of the K(V)2 channel family to modify their functional properties. The localization and functional roles of these silent subunits remain poorly understood. Mutations in the KVS subunit, K(V)8.2 (KCNV2), lead to severe visual impairment in humans, but the basis of these deficits remains unclear. Here, we examined the localization, native interactions, and functional properties of K(V)8.2-containing channels in mouse, macaque, and human photoreceptors of either sex. In human retina, K(V)8.2 colocalized with K(V)2.1 and K(V)2.2 in cone inner segments and with K(V)2.1 in rod inner segments. K(V)2.1 and K(V)2.2 could be coimmunoprecipitated with K(V)8.2 in retinal lysates indicating that these subunits likely interact directly. Retinal K(V)2.1 was less phosphorylated than cortical K(V)2.1, a difference expected to alter the biophysical properties of these channels. Using voltage-clamp recordings and pharmacology, we provide functional evidence for Kv2-containing channels in primate rods and cones. We propose that the presence of K(V)8.2, and low levels of K(V)2.1 phosphorylation shift the activation range of K(V)2 channels to align with the operating range of rod and cone photoreceptors. Our data indicate a role for K(V)2/K(V)8.2 channels in human photoreceptor function and suggest that the visual deficits in patients with KCNV2 mutations arise from inadequate resting activation of K-V channels in rod and cone inner segments.