Effect of ZnCl₂ and Chelation of Zinc Ions by N,N-Diethyldithiocarbamate (DEDTC) on the ERG b-Wave Amplitude from the Isolated Superfused Vertebrate Retina

Abstract

Purpose: NiCl₂ (15 µM) enhances the ERG b-wave amplitude of vertebrate retina, up to 1.5-fold by blocking E/R-type voltage-gated Ca²⁺ channels, which is mediated by blocking the release of GABA onto ionotropic GABA-A and GABA-C receptors. In vivo, it is likely that zinc, rather than nickel ions, may be involved in the modulation of retinal signalling. Therefore, we tested the effect of both, ZnCl₂ (10 to 500 µM) and DEDTC (100 to 500 µM), which chelates zinc ions for the capacity to influence the ERG b-wave amplitude.

Methods: Transretinal potentials from the isolated bovine retina were recorded as electroretinograms and Ca²⁺ inward currents by patch-clamp recordings of stably Ca_v2.3 transfected HEK-293 cells, yielding an IC₅₀ value of 5.3 µM for ZnCl₂.

Results: ZnCl₂ (10–15 µM) increased the b-wave amplitude by 1.52-fold ± 0.12 (n = 6 retinas), which was partially reversible upon washout. The same 1.5-fold stimulation of the b-wave amplitude was reported recently for 15 µM NiCl₂. The superfusion of isolated retinas by DEDTC (100 µM) caused a transient decrease of the ERG b-wave amplitude (0.75-fold ± 0.06; n = 4), suggesting that the co-secretion of Zn²⁺ ions may occur under scotopic conditions.

Conclusion: The stimulatory effect of ZnCl₂ on the ERG b-wave amplitude resembles the stimulatory effect of NiCl₂ and may be mediated rather by the NiCl₂-sensitive, Ca_v2.3 E-/R-type voltage-gated Ca²⁺ channels than by NiCl₂-sensitive T-type channels.

KEYWORDS::

• Ca_v2.3
• Isolated and superfused retina
• Pharmacoresistant
• Reciprocal inhibition
• R-type
• Voltage-gated Ca²⁺ channels

ACKNOWLEDGMENTS

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

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.