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Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2312-24. doi: 10.1167/iovs.15-16654.

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

Author information

1
Institute of Anatomy and Cell Biology, Department of Neuroanatomy, Saarland University School of Medicine, Homburg, Germany.
2
Department of Pharmacology and Toxicology, Saarland University School of Medicine, Homburg, Germany.
3
Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard Karls University, Tübingen, Germany.

Abstract

PURPOSE:

The cacnb2 gene encodes the β2 subunit (Cavβ2) 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 Cavβ2.

METHODS:

A cacnb2-deficient mouse strain was generated and deletion of the Cavβ2 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 Cavβ2 studied by depolarization-induced Ca2+ influx into isolated photoreceptor cells and electroretinography.

RESULTS:

Voltage-gated Ca2+ influx into rod photoreceptors lacking Cavβ2 was abolished and the typical rod ribbon-type active zones were absent in Cavβ2-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 Cavβ2-deficient retinas.

CONCLUSIONS:

The presence of the Cavβ2 is essential for the structural integrity and function of the rod photoreceptor synapse. The Cavβ2 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 Cavβ2-deficient retinas.

PMID:
25766584
DOI:
10.1167/iovs.15-16654
[Indexed for MEDLINE]

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