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Publication : Submicromolar copper (II) ions stimulate transretinal signaling in the isolated retina from wild type but not from Ca(v)2.3-deficient mice.

First Author  Lüke JN Year  2020
Journal  BMC Ophthalmol Volume  20
Issue  1 Pages  182
PubMed ID  32375703 Mgi Jnum  J:337340
Mgi Id  MGI:6728599 Doi  10.1186/s12886-020-01451-8
Citation  Luke JN, et al. (2020) Submicromolar copper (II) ions stimulate transretinal signaling in the isolated retina from wild type but not from Cav2.3-deficient mice. BMC Ophthalmol 20(1):182
abstractText  BACKGROUND: So far, only indirect evidence exists for the pharmacoresistant R-type voltage-gated Ca(2+) 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 Ni(2+), Zn(2+) and Cu(2+). To further confirm the interpretation of these findings, we compared the effects of Cu(2+) 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 muM 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: Cu(2+)-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 Ca(2+) channels are involved in shaping transretinal responses during light perception.
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