Two separate Ni2+‐sensitive voltage‐gated Ca2+channels modulate transretinal signalling in the isolated murine retina

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 NiCl₂‐sensitive component was attributed to reciprocal signalling by pharmacoresistant R‐type voltage‐gated Ca²⁺ channels, which similar to other voltage‐dependent Ca²⁺ channels trigger and control neurotransmitter release. The murine retina has the great advantage that the effect of gene inactivation for Ni²⁺‐sensitive Ca²⁺ channels can be analysed to prove or disprove that any of these Ca²⁺ channels is involved in retinal signalling. Methods: Superfused retinas from different murine genotypes lacking either one or both highly Ni²⁺‐sensitive voltage‐gated Ca²⁺ 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 Ca²⁺ channels were superfused with a NiCl₂ (15 μm ) containing nutrient solution. The change in the b‐wave amplitude and implicit time, caused by NiCl₂, 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 Ni²⁺‐mediated increase in the b‐wave amplitude is significantly increased, probably due to a loss of reciprocal inhibition to photoreceptors. Thus, each of the Ni²⁺‐sensitive Ca²⁺ channels contributes to specific features of the b‐wave response. Conclusion: Both high‐affinity Ni²⁺‐sensitive Ca²⁺ channels contribute to transretinal signalling. Based on the results from the double knockout mice, additional targets for NiCl₂ must contribute to transretinal signalling, which will be most important for the structurally similar physiologically more important heavy metal cation Zn²⁺.