Submicromolar copper (II) ions stimulate transretinal signaling in the isolated retina from wild type but not from Cav2.3-deficient mice

• DOI: 10.21203/rs.2.16907/v4
• Publication Date: 2020-04-20T17:33:27Z
• Authors: Jan Niklas Lüke; Felix Neumaier; Serdar Alpdogan; Jürgen Hescheler; Toni Schneider; Walid Albanna; Isha Akhtar-Schäfer
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; 0303 health sciences; B-wave; Calcium Channels, R-Type; RE1-994; Isolated vertebrate retina; Retina; Ophthalmology; Mice; 03 medical and health sciences; Reverse inhibition; Models, Animal; Electroretinography; Murine ERG; Animals; Cation Transport Proteins; Copper; Photic Stimulation; Research Article; Signal Transduction

Abstract Background: So far, only indirect evidence exists for the pharmacoresistant R-type voltage-gated Ca2+ channel (VGCC) to be involved in transretinal signaling by triggering GABA-release onto ON-bipolar neurons. This release of inhibitory neurotransmitters was deduced from the sensitivity of the b-wave to stimulation by Ni2+, Zn2+ and Cu2+. To further confirm the interpretation of these findings, we compared the effects of Cu2+ application and chelation (using kainic acid, KA) on the neural retina from wildtype and Cav2.3-deficient mice. Furthermore, the immediately effect of KA on the ERG b-wave modulation was assessed.Methods: Transretinal signaling was recorded as an ERG from the superfused murine retina isolated from wildtype and Cav2.3-deficient mice.Results: In mice, the stimulating effect of 100 nM CuCl2 is absent in the retinae from Cav2.3-deficient mice, but prominent in Cav2.3-competent mice. Application of up to 3 mM tricine does not affect the murine b-wave in both genotypes, most likely because of chelating amino acids present in the murine nutrient solution. Application of 27 µM KA significantly increased the b-wave amplitude in wild type and Cav2.3 (-|-) mice. This effect can most likely be explained by the stimulation of endogenous KA-receptors described in horizontal, OFF-bipolar, amacrine or ganglion cells, which could not be fully blocked in the present study.Conclusion: Cu2+-dependent modulation of transretinal signaling only occurs in the murine retina from Cav2.3 competent mice, supporting the ideas derived from previous work in the bovine retina that R-type Ca2+ channels are involved in shaping transretinal responses during light perception.