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Low concentrations of ethanol but not of dimethyl sulfoxide (DMSO) impair reciprocal retinal signal transduction

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Abstract

Background

The model of the isolated and superfused retina provides the opportunity to test drugs and toxins. Some chemicals have to be applied using low concentrations of organic solvents as carriers. Recently, E-/R-type (Cav2.3) and T-type (Cav3.2) voltage-gated Ca2+ channels were identified as participating in reciprocal inhibitory retinal signaling. Their participation is apparent, when low concentrations of NiCl2 (15 μM) are applied during superfusion leading to an increase of the ERG b-wave amplitude, which is explained by a reduction of amacrine GABA-release onto bipolar neurons. During these investigations, differences were observed for the solvent carrier used.

Methods

Recording of the transretinal receptor potentials from the isolated bovine retina.

Results

The pretreatment of bovine retina with 0.01 % (v/v) dimethylsulfoxide did not impair the NiCl2-mediated increase of the b-wave amplitude, which was 1.31-fold ± 0.03 of initial value (n = 4). However, pretreatment of the retina with the same concentration of ethanol impaired reciprocal signaling (0.96-fold ± 0.05, n = 4). Further, the implicit time of the b-wave was increased, suggesting that ethanol itself but not DMSO may antagonize GABA-receptors.

Conclusion

Ethanol itself but not DMSO may block GABA receptors and cause an amplitude increase by itself, so that reciprocal signaling is impaired.

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Acknowledgments

The work was financially supported by the Köln Fortune Program/Faculty of Medicine, University of Köln and the Center of Molecular Medicine Cologne/Zentrum für Molekulare Medizin Köln (Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie, Förderkennzeichen 01 KS 9502, to TS and JH).

Conflicts of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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Authors and Affiliations

  1. Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, D-50931, Köln, Germany

    Siarhei A. Siapich, Isha Akhtar, Jürgen Hescheler, Toni Schneider & Matthias Lüke

  2. Department of Ophthalmology, RWTH Aachen University, Pauwelsstr. 30, D-52074, Aachen, Germany

    Siarhei A. Siapich

  3. University Eye Hospital, University of Lübeck, Ratzeburger Allee 160, D-23538, Lübeck, Germany

    Matthias Lüke

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  1. Siarhei A. Siapich
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Correspondence to Toni Schneider.

Additional information

Toni Schneider and Matthias Lüke contributed equally to senior authorship.

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Supplemental figure

ERG recordings under scotopic conditions (stimulus light intensity 6.3 mlx for 0.5 sec, every 5 min). Mean values of this experiment are included in Table 2 as experiment #5. a Time course of the b-wave amplitude before and during adding 0.01 % ethanol to the standard nutrition solution. Note, the amplitude increases by ethanol from 17.4 ± 0.5 μV (n = 10 ERG traces) to 22.4 ± 0.3 μV (n = 10), which represents a 1.29-fold increase, which normally would be expected to be caused by NiCl2 (15 μM). Even when ethanol was washed out, no NiCl2-mediated increase was observed. The slight reduction of the b-wave after nearly 5 hours of incubation may be due to the length of the experiment. The numbers #1 to #5 correspond to individual ERG traces as shown in panels c1 to c5. b Time course of the implicit time for each of the conditions described in a and as indicated by the information bar in both panels. Note, the implicit time starts to increase over time under ethanol and increases again and even stronger under NiCl2 (15 μM). c Individual ERG traces, which were recorded under the conditions as shown in a and as described in each subpanel # c1 to # c5. The amplitudes do not change, but the implicit times get longer over time. (PPTX 1540 kb)

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Siapich, S.A., Akhtar, I., Hescheler, J. et al. Low concentrations of ethanol but not of dimethyl sulfoxide (DMSO) impair reciprocal retinal signal transduction. Graefes Arch Clin Exp Ophthalmol 253, 1713–1719 (2015). https://doi.org/10.1007/s00417-015-3070-7

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