AUTHOR=Shi Liheng , Chang Janet Ya-An , Yu Fei , Ko Michael L. , Ko Gladys Y.-P. 

TITLE=The Contribution of L-Type Cav1.3 Channels to Retinal Light Responses

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=10

YEAR=2017

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2017.00394

DOI=10.3389/fnmol.2017.00394

ISSN=1662-5099

ABSTRACT=<p>L-type voltage-gated calcium channels (LTCCs) regulate tonic neurotransmitter release from sensory neurons including retinal photoreceptors. There are three types of LTCCs (Ca<sub>v</sub>1.2, Ca<sub>v</sub>1.3, and Ca<sub>v</sub>1.4) expressed in the retina. While Ca<sub>v</sub>1.2 is expressed in all retinal cells including the Müller glia and neurons, Ca<sub>v</sub>1.3 and Ca<sub>v</sub>1.4 are expressed in the retinal neurons with Ca<sub>v</sub>1.4 exclusively expressed in the photoreceptor synaptic terminals. Mutations in the gene encoding Ca<sub>v</sub>1.4 cause incomplete X-linked congenital stationary night blindness in humans. Even though Ca<sub>v</sub>1.3 is present in the photoreceptor inner segments and the synaptic terminals in various vertebrate species, its role in vision is unclear, since genetic alterations in Ca<sub>v</sub>1.3 are not associated with severe vision impairment in humans or in Ca<sub>v</sub>1.3-null (Ca<sub>v</sub>1.3<sup>−/−</sup>) mice. However, a failure to regulate Ca<sub>v</sub>1.3 was found in a mouse model of Usher syndrome, the most common cause of combined deafness and blindness in humans, indicating that Ca<sub>v</sub>1.3 may contribute to retinal function. In this report, we combined physiological and morphological data to demonstrate the role of Ca<sub>v</sub>1.3 in retinal physiology and function that has been undervalued thus far. Through <italic>ex vivo</italic> and <italic>in vivo</italic> electroretinogram (ERG) recordings and immunohistochemical staining, we found that Ca<sub>v</sub>1.3 plays a role in retinal light responses and synaptic plasticity. Pharmacological inhibition of Ca<sub>v</sub>1.3 decreased <italic>ex vivo</italic> ERG a- and b-wave amplitudes. In Ca<sub>v</sub>1.3<sup>−/−</sup> mice, their dark-adapted ERG a-, b-wave, and oscillatory potential amplitudes were significantly dampened, and implicit times were delayed compared to the wild type (WT). Furthermore, the density of ribbon synapses was reduced in the outer plexiform layer of Ca<sub>v</sub>1.3<sup>−/−</sup> mice retinas. Hence, Ca<sub>v</sub>1.3 plays a more prominent role in retinal physiology and function than previously reported.</p>