The Contribution of L-Type Ca_v1.3 Channels to Retinal Light Responses

L-type voltage-gated calcium channels (LTCCs) regulate tonic neurotransmitter release from sensory neurons including retinal photoreceptors. There are three types of LTCCs (Ca_v1.2, Ca_v1.3, and Ca_v1.4) expressed in the retina. While Ca_v1.2 is expressed in all retinal cells including the Müller glia and neurons, Ca_v1.3 and Ca_v1.4 are expressed in the retinal neurons with Ca_v1.4 exclusively expressed in the photoreceptor synaptic terminals. Mutations in the gene encoding Ca_v1.4 cause incomplete X-linked congenital stationary night blindness in humans. Even though Ca_v1.3 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_v1.3 are not associated with severe vision impairment in humans or in Ca_v1.3-null (Ca_v1.3^-/-) mice. However, a failure to regulate Ca_v1.3 was found in a mouse model of Usher syndrome, the most common cause of combined deafness and blindness in humans, indicating that Ca_v1.3 may contribute to retinal function. In this report, we combined physiological and morphological data to demonstrate the role of Ca_v1.3 in retinal physiology and function that has been undervalued thus far. Through ex vivo and in vivo electroretinogram (ERG) recordings and immunohistochemical staining, we found that Ca_v1.3 plays a role in retinal light responses and synaptic plasticity. Pharmacological inhibition of Ca_v1.3 decreased ex vivo ERG a- and b-wave amplitudes. In Ca_v1.3^-/- 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_v1.3^-/- mice retinas. Hence, Ca_v1.3 plays a more prominent role in retinal physiology and function than previously reported.