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

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 Ca(v)2.3-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 Ca(v)2.3-deficient mice. RESULTS: In mice, the stimulating effect of 100 nM CuCl(2) is absent in the retinae from Ca(v)2.3-deficient mice, but prominent in Ca(v)2.3-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 Ca(v)2.3 (−|-) 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 Ca(v)2.3 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.