Figure 3.

Simplified schematic representation highlighting the targets studied. Illustration of the retina and support circulations (using conventions in Fig. 1), including the HCs.^66–68 In the dark, rod cell membranes are depolarized, resulting in the sustained opening of synaptic LTCCs of the Ca_v1.4 subtype and presumably Ca_v1.3 LTCCs in rod nuclei.^4–6 Persistent opening of Ca_v1.4 channels (but not, apparently, Ca_v1.3 LTCCs) triggers continuous release of the neurotransmitter glutamate, a process regulated by arrestin-1.^7,8 When HCs receive glutamatergic input, their membranes depolarize and send (by a yet unclear process) inhibitory signals back to the photoreceptors.^9,10 The present data suggest that the target proteins chosen (based on light-based studies ex vivo) also participate in inhibitory signaling in mice in total darkness in vivo when HCs experience a maximum and sustained glutamate exposure.