Role of the β₂ subunit of voltage-dependent calcium channels in the retinal outer plexiform layer

PURPOSE. Mutations in the α_1F subunit of voltage-dependent calcium channels (VDCCs) have been shown to cause incomplete congenital stationary night blindness (CSNB2). The purpose of this study was to identify which of the four β subunits of VDCCs participates in the formation of this channel at the photoreceptor synapse and to determine how its absence affects visual processing. METHODS. Mice without each of the four known β subunits of VDCCs were generated by gene targeting and transgenic rescue (CNS-β₁, -β₂) or by gene targeting alone (β₃) or were obtained from a commercial provider (β₄). Retinal function and visual sensitivity were examined by electroretinography and an active avoidance behavioral test, respectively. The structure of the retina and expression of the α_-F subunit were examined at the light microscopic level and by immunohistochemistry. RESULTS. Under dark-adapted conditions, CNS-β₂-null mice had a normal ERG a-wave, but did not have a normal b-wave. In addition, these mice showed decreased sensitivity to light. Both the a- and b-waves appear normal in the CNS-β₁-, β₃-, and β₄-null mice. Histologic analyses of all four mouse lines indicated that only the CNS-β₂-null mice had altered retinal morphology. Eyes of these mice had a thinner outer plexiform layer (OPL) than eyes of control animals. In addition, the labeling pattern of the α_1F subunit in the OPL was altered in CNS-β₂-null mice. CONCLUSIONS. The normal distribution of the α_1F subunit of the VDCCs in the OPL is dependent on the expression of the β₂ subunit. The expression of both of these subunits is required for normal maintenance and/or formation of the OPL and synaptic transmission.