The contribution of L-type CaV 1.3 channels to retinal light responses

Abstract

L-type voltage-gated calcium channels (LTCCs) regulate tonic neurotransmitter release from sensory neurons including retinal photoreceptors. There are three types of LTCCs (Cav 1.2, Cav 1.3, and Cav 1.4) expressed in the retina. While Cav 1.2 is expressed in all retinal cells including the Müller glia and neurons, Cav 1.3 and Cav 1.4 are expressed in the retinal neurons with Cav 1.4 exclusively expressed in the photoreceptor synaptic terminals. Mutations in the gene encoding Cav 1.4 cause incomplete X-linked congenital stationary night blindness in humans. Even though Cav 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 Cav 1.3 are not associated with severe vision impairment in humans or in Cav 1.3-null (Cav 1.3−/−) mice. However, a failure to regulate Cav 1.3 was found in a mouse model of Usher syndrome, the most common cause of combined deafness and blindness in humans, indicating that Cav 1.3 may contribute to retinal function. In this report, we combined physiological and morphological data to demonstrate the role of Cav 1.3 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 Cav 1.3 plays a role in retinal light responses and synaptic plasticity. Pharmacological inhibition of Cav 1.3 decreased ex vivo ERGa- and b-wave amplitudes. In Cav 1.3−/− mice, their dark-adapted ERGa-, 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 plexiformlayer of Cav 1.3−/− mice retinas. Hence, Cav 1.3 plays a more prominent role in retinal physiology and function than previously reported.