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

Zanetti L, Kilicarslan I, Netzer M, Babai N, Seitter H, Koschak A (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 11

Article Number: 2732

Journal Issue: 1

DOI: 10.1038/s41598-021-82210-7

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.

Authors with CRIS profile

Zsolt Norbert Babai Lehrstuhl für Tierphysiologie

Involved external institutions

Leopold-Franzens-Universität Innsbruck / University of Innsbruck AT Austria (AT)

How to cite

APA:

Zanetti, L., Kilicarslan, I., Netzer, M., Babai, N., Seitter, H., & Koschak, A. (2021). Function of cone and cone-related pathways in CaV1.4 IT mice. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-82210-7

MLA:

Zanetti, Lucia, et al. "Function of cone and cone-related pathways in CaV1.4 IT mice." Scientific Reports 11.1 (2021).

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