Using mutant mice to study the role of voltage-gated calcium channels in the retina.
Neuronal voltage-gated calcium channels (VGCCs) are critical to numerous cellular functions including synaptogenesis and neurotransmitter release. Mutations in individual subunits of VGCCs are known to result in a wide array of neurological disorders including episodic ataxia, epilepsy, and migraines. The characterization of these disorders has focused on channel function within the brain. However, a defect in the retina-specific alpha1F subunit of an L-type VGCC results is a loss of visual sensitivity or the incomplete form of X-linked congenital stationary night blindness (CSNB2). Based on the electroretinographic phenotype of these patients this channel type is localized to the axon terminal of photoreceptor cells and results in a loss of signal transmission from photoreceptors to bipolar cells. A mouse with a deletion of the beta2 subunit of VGCCs in the central nervous system was recently shown to have a similar phenotype as CSNB2 patients. The identification of the role of VGCCs in this disorder highlights the potential association of other VGCC mutations with retinal disorders. The study of the role of these channels in normal retinal function may also be elucidated by the characterization of retinal structure and visual function in the numerous knockout, transgenic, and naturally occurring mouse mutants currently available.
Ball
Sherry L
SL
Research Service, Cleveland VA Medical Center, 10701 East Boulevard, Cleveland, OH 44106, USA.
Gregg
Ronald G
RG
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
D015220:Calcium Channels; D002118:Calcium