Heteromeric K_V2/K_V8.2 channels mediate delayed rectifier potassium currents in primate photoreceptors

Silent voltage-gated potassium channel subunits (K^VS) interact selectively with members of the K^V2 channel family to modify their functional properties. The localization and functional roles of these silent subunits remain poorly understood. Mutations in the K^VS subunit, K^V8.2 (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^V8.2-containing channels in mouse, macaque, and human photoreceptors of either sex. In human retina, K^V8.2 colocalized with K^V2.1 and K^V2.2 in cone inner segments and with K^V2.1 in rod inner segments. K^V2.1 and K^V2.2 could be coimmunoprecipitated with K^V8.2 in retinal lysates indicating that these subunits likely interact directly. Retinal K^V2.1 was less phosphorylated than cortical K^V2.1, a difference expected to alter the biophysical properties of these channels. Using voltage-clamp recordings and pharmacology, we provide functional evidence for K^V2-containing channels in primate rods and cones.Wepropose that the presence ofK^V8.2, and low levels ofK^V2.1 phosphorylation shift the activation range ofK^V2 channels to align with the operating range of rod and cone photoreceptors. Our data indicate a role forK^V2/K^V8.2 channels inhumanphotoreceptor 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.