The Contribution of L-Type Ca1.3 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 (Ca1.2, Ca1.3, and Ca1.4) expressed in the retina. While Ca1.2 is expressed in all retinal cells including the Müller glia and neurons, Ca1.3 and Ca1.4 are expressed in the retinal neurons with Ca1.4 exclusively expressed in the photoreceptor synaptic terminals. Mutations in the gene encoding Ca1.4 cause incomplete X-linked congenital stationary night blindness in humans. Even though Ca1.3 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 Ca1.3 are not associated with severe vision impairment in humans or in Ca1.3-null (Ca1.3) mice. However, a failure to regulate Ca1.3 was found in a mouse model of Usher syndrome, the most common cause of combined deafness and blindness in humans, indicating that Ca1.3 may contribute to retinal function. In this report, we combined physiological and morphological data to demonstrate the role of Ca1.3 in retinal physiology and function that has been undervalued thus far. Through and electroretinogram (ERG) recordings and immunohistochemical staining, we found that Ca1.3 plays a role in retinal light responses and synaptic plasticity. Pharmacological inhibition of Ca1.3 decreased ERG a- and b-wave amplitudes. In Ca1.3 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 Ca1.3 mice retinas. Hence, Ca1.3 plays a more prominent role in retinal physiology and function than previously reported.