Function of cone and cone-related pathways in CaV1.4 IT mice

Abstract CaV1.4 L-type calcium channels are predominantly expressed in photoreceptor terminals playing a crucial role for synaptic transmission and, consequently, for vision. Human mutations in the encoding gene are associated with congenital stationary night blindness type-2. Besides rod-driven sco...

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Autores principales:	Lucia Zanetti, Irem Kilicarslan, Michael Netzer, Norbert Babai, Hartwig Seitter, Alexandra Koschak
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bae152107bcb4000819c34d09136ac31
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spelling	oai:doaj.org-article:bae152107bcb4000819c34d09136ac312021-12-02T14:06:50ZFunction of cone and cone-related pathways in CaV1.4 IT mice10.1038/s41598-021-82210-72045-2322https://doaj.org/article/bae152107bcb4000819c34d09136ac312021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82210-7https://doaj.org/toc/2045-2322Abstract CaV1.4 L-type calcium channels are predominantly expressed in photoreceptor terminals playing a crucial role for synaptic transmission and, consequently, for vision. Human mutations in the encoding gene are associated with congenital stationary night blindness type-2. Besides rod-driven scotopic vision also cone-driven photopic responses are severely affected in patients. The present study therefore examined functional and morphological changes in cones and cone-related pathways in mice carrying the CaV1.4 gain-of function mutation I756T (CaV1.4-IT) using multielectrode array, patch-clamp and immunohistochemical analyses. CaV1.4-IT ganglion cell responses to photopic stimuli were seen only in a small fraction of cells indicative of a major impairment in the cone pathway. Though cone photoreceptors underwent morphological rearrangements, they retained their ability to release glutamate. Our functional data suggested a postsynaptic cone bipolar cell defect, supported by the fact that the majority of cone bipolar cells showed sprouting, while horizontal cells maintained contacts with cones and cone-to-horizontal cell input was preserved. Furthermore a reduction of basal Ca2+ influx by a calcium channel blocker was not sufficient to rescue synaptic transmission deficits caused by the CaV1.4-IT mutation. Long term treatments with low-dose Ca2+ channel blockers might however be beneficial reducing Ca2+ toxicity without major effects on ganglion cells responses.Lucia ZanettiIrem KilicarslanMichael NetzerNorbert BabaiHartwig SeitterAlexandra KoschakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lucia Zanetti Irem Kilicarslan Michael Netzer Norbert Babai Hartwig Seitter Alexandra Koschak Function of cone and cone-related pathways in CaV1.4 IT mice
description	Abstract CaV1.4 L-type calcium channels are predominantly expressed in photoreceptor terminals playing a crucial role for synaptic transmission and, consequently, for vision. Human mutations in the encoding gene are associated with congenital stationary night blindness type-2. Besides rod-driven scotopic vision also cone-driven photopic responses are severely affected in patients. The present study therefore examined functional and morphological changes in cones and cone-related pathways in mice carrying the CaV1.4 gain-of function mutation I756T (CaV1.4-IT) using multielectrode array, patch-clamp and immunohistochemical analyses. CaV1.4-IT ganglion cell responses to photopic stimuli were seen only in a small fraction of cells indicative of a major impairment in the cone pathway. Though cone photoreceptors underwent morphological rearrangements, they retained their ability to release glutamate. Our functional data suggested a postsynaptic cone bipolar cell defect, supported by the fact that the majority of cone bipolar cells showed sprouting, while horizontal cells maintained contacts with cones and cone-to-horizontal cell input was preserved. Furthermore a reduction of basal Ca2+ influx by a calcium channel blocker was not sufficient to rescue synaptic transmission deficits caused by the CaV1.4-IT mutation. Long term treatments with low-dose Ca2+ channel blockers might however be beneficial reducing Ca2+ toxicity without major effects on ganglion cells responses.
format	article
author	Lucia Zanetti Irem Kilicarslan Michael Netzer Norbert Babai Hartwig Seitter Alexandra Koschak
author_facet	Lucia Zanetti Irem Kilicarslan Michael Netzer Norbert Babai Hartwig Seitter Alexandra Koschak
author_sort	Lucia Zanetti
title	Function of cone and cone-related pathways in CaV1.4 IT mice
title_short	Function of cone and cone-related pathways in CaV1.4 IT mice
title_full	Function of cone and cone-related pathways in CaV1.4 IT mice
title_fullStr	Function of cone and cone-related pathways in CaV1.4 IT mice
title_full_unstemmed	Function of cone and cone-related pathways in CaV1.4 IT mice
title_sort	function of cone and cone-related pathways in cav1.4 it mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bae152107bcb4000819c34d09136ac31
work_keys_str_mv	AT luciazanetti functionofconeandconerelatedpathwaysincav14itmice AT iremkilicarslan functionofconeandconerelatedpathwaysincav14itmice AT michaelnetzer functionofconeandconerelatedpathwaysincav14itmice AT norbertbabai functionofconeandconerelatedpathwaysincav14itmice AT hartwigseitter functionofconeandconerelatedpathwaysincav14itmice AT alexandrakoschak functionofconeandconerelatedpathwaysincav14itmice
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Function of cone and cone-related pathways in CaV1.4 IT mice

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