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Cav1.4 dysfunction and congenital stationary night blindness type 2
- Source :
- Pflugers Archiv
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Cav1.4 L-type Ca2+ channels are predominantly expressed in retinal neurons, particularly at the photoreceptor terminals where they mediate sustained Ca2+ entry needed for continuous neurotransmitter release at their ribbon synapses. Cav1.4 channel gating properties are controlled by accessory subunits, associated regulatory proteins, and also alternative splicing. In humans, mutations in the CACNA1F gene encoding for Cav1.4 channels are associated with X-linked retinal disorders such as congenital stationary night blindness type 2. Mutations in the Cav1.4 protein result in a spectrum of altered functional channel activity. Several mouse models broadened our understanding of the role of Cav1.4 channels not only as Ca2+ source at retinal synapses but also as synaptic organizers. In this review, we highlight different structural and functional phenotypes of Cav1.4 mutations that might also occur in patients with congenital stationary night blindness type 2. A further important yet mostly neglected aspect that we discuss is the influence of alternative splicing on channel dysfunction. We conclude that currently available functional phenotyping strategies should be refined and summarize potential specific therapeutic options for patients carrying Cav1.4 mutations. Importantly, the development of new therapeutic approaches will permit a deeper understanding of not only the disease pathophysiology but also the physiological function of Cav1.4 channels in the retina.
- Subjects :
- 0301 basic medicine
Retinal Disorder
Calcium Channels, L-Type
Physiology
Clinical Biochemistry
Ribbon synapse
Biology
Retina
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Channelopathy
Night Blindness
Channel modulation
Physiology (medical)
Myopia
medicine
Animals
Humans
Congenital stationary night blindness
Calcium channel
Alternative splicing
Congenital stationary night blindness type 2
Eye Diseases, Hereditary
Genetic Diseases, X-Linked
Retinal
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
medicine.disease
Calcium Channel Agonists
Cav1.4
030104 developmental biology
medicine.anatomical_structure
chemistry
Retinal disease
Mutation
Synapses
Original Article
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14322013 and 00316768
- Volume :
- 473
- Database :
- OpenAIRE
- Journal :
- Pflügers Archiv - European Journal of Physiology
- Accession number :
- edsair.doi.dedup.....c948bff7983ce634eb674e4898eced48