Influence of the β2-Subunit of L-Type Voltage-Gated Cav Channels on the Structural and Functional Development of Photoreceptor Ribbon Synapses

PURPOSE. The cacnb2 gene encodes the beta 2 subunit (Cav beta 2) of voltage-gated Ca2+ channels in photoreceptors, and its targeted deletion in mice has previously been shown to cause altered retinal morphology and synaptic transmission. The purpose of this study was to provide a detailed morphologic study combined with experiments on the altered functions of photoreceptor ribbon synapses lacking Cav beta 2. METHODS. A cacnb2-deficient mouse strain was generated and deletion of the Cav beta 2 in the retina documented by biochemical and immunhistochemical approaches. Ultrastructural changes of photoreceptor ribbon synapses were examined by electronmicroscopy and functional implications of the lack of Cav beta 2 studied by depolarization-induced Ca2+ influx into isolated photoreceptor cells and electroretinography. RESULTS. Voltage-gated Ca2+ influx into rod photoreceptors lacking Cav beta 2 was abolished and the typical rod ribbon-type active zones were absent in Cav beta 2-deficient retinas. The active zone and the architecture of the presynaptic terminals were severely altered in rod synapses. Cone photoreceptor and the bipolar cell ribbon synapses were largely spared from ultrastructural changes although peanut agglutinin (PNA) labelling and photopic ERG analyses demonstrated that also cone pathways were disturbed in Cav beta 2-deficient retinas. CONCLUSIONS. The presence of the Cav beta 2 is essential for the structural integrity and function of the rod photoreceptor synapse. The Cav beta 2 is less essential for the morphology of cone and bipolar cell ribbon synapses, although the impaired photopic electroretinogram suggests a functional alteration also of the cone-mediated signaling in Cav beta 2-deficient retinas.