Two separate Ni 2+-sensitive voltage-gated Ca 2+channels modulate transretinal signalling in the isolated murine retina

Abstract

Purpose: Light-evoked responses from vertebrate retinas were recorded as an electroretinogram (ERG). The b-wave is the most prominent component of the ERG, and in the bovine retina its NiCl 2-sensitive component was attributed to reciprocal signalling by pharmacoresistant R-type voltage-gated Ca 2+ channels, which similar to other voltage-dependent Ca 2+ channels trigger and control neurotransmitter release. The murine retina has the great advantage that the effect of gene inactivation for Ni 2+-sensitive Ca 2+ channels can be analysed to prove or disprove that any of these Ca 2+ channels is involved in retinal signalling. Methods: Superfused retinas from different murine genotypes lacking either one or both highly Ni 2+-sensitive voltage-gated Ca 2+ channels were used to record their ex vivo ERGs. Results: The isolated retinas from mice lacking Ca v2.3 R-type or Ca v3.2 T-type or both voltage-gated Ca 2+ channels were superfused with a NiCl 2 (15 μm) containing nutrient solution. The change in the b-wave amplitude and implicit time, caused by NiCl 2, was calculated as a difference spectrum and compared to data from control animals. From the results, it can be deduced that Ca v2.3 contributes rather to a later component in the b-wave response, while in the absence of Ca v3.2 the gain of Ni 2+-mediated increase in the b-wave amplitude is significantly increased, probably due to a loss of reciprocal inhibition to photoreceptors. Thus, each of the Ni 2+-sensitive Ca 2+ channels contributes to specific features of the b-wave response. Conclusion: Both high-affinity Ni 2+-sensitive Ca 2+ channels contribute to transretinal signalling. Based on the results from the double knockout mice, additional targets for NiCl 2 must contribute to transretinal signalling, which will be most important for the structurally similar physiologically more important heavy metal cation Zn 2+. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.