The Contribution of L-Type Cav1.3 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 (Cav1.2, Cav1.3, and Cav1.4) expressed in the retina. While Cav1.2 is expressed in all retinal cells including the Müller glia a...

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Main Authors: Liheng Shi, Janet Ya-An Chang, Fei Yu, Michael L. Ko, Gladys Y.-P. Ko
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-12-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fnmol.2017.00394/full
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author Liheng Shi
Janet Ya-An Chang
Fei Yu
Michael L. Ko
Gladys Y.-P. Ko
Gladys Y.-P. Ko
author_facet Liheng Shi
Janet Ya-An Chang
Fei Yu
Michael L. Ko
Gladys Y.-P. Ko
Gladys Y.-P. Ko
author_sort Liheng Shi
collection DOAJ
description L-type voltage-gated calcium channels (LTCCs) regulate tonic neurotransmitter release from sensory neurons including retinal photoreceptors. There are three types of LTCCs (Cav1.2, Cav1.3, and Cav1.4) expressed in the retina. While Cav1.2 is expressed in all retinal cells including the Müller glia and neurons, Cav1.3 and Cav1.4 are expressed in the retinal neurons with Cav1.4 exclusively expressed in the photoreceptor synaptic terminals. Mutations in the gene encoding Cav1.4 cause incomplete X-linked congenital stationary night blindness in humans. Even though Cav1.3 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 Cav1.3 are not associated with severe vision impairment in humans or in Cav1.3-null (Cav1.3−/−) mice. However, a failure to regulate Cav1.3 was found in a mouse model of Usher syndrome, the most common cause of combined deafness and blindness in humans, indicating that Cav1.3 may contribute to retinal function. In this report, we combined physiological and morphological data to demonstrate the role of Cav1.3 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 Cav1.3 plays a role in retinal light responses and synaptic plasticity. Pharmacological inhibition of Cav1.3 decreased ex vivo ERG a- and b-wave amplitudes. In Cav1.3−/− 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 Cav1.3−/− mice retinas. Hence, Cav1.3 plays a more prominent role in retinal physiology and function than previously reported.
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spelling doaj.art-bd40e214238e4657b65233465e8441db2022-12-21T19:10:34ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-12-011010.3389/fnmol.2017.00394293615The Contribution of L-Type Cav1.3 Channels to Retinal Light ResponsesLiheng Shi0Janet Ya-An Chang1Fei Yu2Michael L. Ko3Gladys Y.-P. Ko4Gladys Y.-P. Ko5Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, United StatesDepartment of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, United StatesDepartment of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, United StatesDepartment of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, United StatesDepartment of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, United StatesTexas A&M Institute of Neuroscience, Texas A&M University, College Station, TX, United StatesL-type voltage-gated calcium channels (LTCCs) regulate tonic neurotransmitter release from sensory neurons including retinal photoreceptors. There are three types of LTCCs (Cav1.2, Cav1.3, and Cav1.4) expressed in the retina. While Cav1.2 is expressed in all retinal cells including the Müller glia and neurons, Cav1.3 and Cav1.4 are expressed in the retinal neurons with Cav1.4 exclusively expressed in the photoreceptor synaptic terminals. Mutations in the gene encoding Cav1.4 cause incomplete X-linked congenital stationary night blindness in humans. Even though Cav1.3 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 Cav1.3 are not associated with severe vision impairment in humans or in Cav1.3-null (Cav1.3−/−) mice. However, a failure to regulate Cav1.3 was found in a mouse model of Usher syndrome, the most common cause of combined deafness and blindness in humans, indicating that Cav1.3 may contribute to retinal function. In this report, we combined physiological and morphological data to demonstrate the role of Cav1.3 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 Cav1.3 plays a role in retinal light responses and synaptic plasticity. Pharmacological inhibition of Cav1.3 decreased ex vivo ERG a- and b-wave amplitudes. In Cav1.3−/− 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 Cav1.3−/− mice retinas. Hence, Cav1.3 plays a more prominent role in retinal physiology and function than previously reported.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00394/fullL-type voltage-gated calcium channelphotoreceptorribbon synapseselectroretinogram
spellingShingle Liheng Shi
Janet Ya-An Chang
Fei Yu
Michael L. Ko
Gladys Y.-P. Ko
Gladys Y.-P. Ko
The Contribution of L-Type Cav1.3 Channels to Retinal Light Responses
Frontiers in Molecular Neuroscience
L-type voltage-gated calcium channel
photoreceptor
ribbon synapses
electroretinogram
title The Contribution of L-Type Cav1.3 Channels to Retinal Light Responses
title_full The Contribution of L-Type Cav1.3 Channels to Retinal Light Responses
title_fullStr The Contribution of L-Type Cav1.3 Channels to Retinal Light Responses
title_full_unstemmed The Contribution of L-Type Cav1.3 Channels to Retinal Light Responses
title_short The Contribution of L-Type Cav1.3 Channels to Retinal Light Responses
title_sort contribution of l type cav1 3 channels to retinal light responses
topic L-type voltage-gated calcium channel
photoreceptor
ribbon synapses
electroretinogram
url http://journal.frontiersin.org/article/10.3389/fnmol.2017.00394/full
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