Transducin Translocation Sensitizes Synaptic Transmission From Rods To Rod Bipolar Cells

Abstract

Purpose: : During exposure to bright light, components of the phototransduction cascade in rod photoreceptors translocate between the outer and inner segments of the cell. In particular, rod transducin (G_αt1) moves to rod inner segments and synaptic terminals in bright light. While the movement of G_αt1 has been suggested to play a role in light adaptation by reducing the sensitivity of phototransduction, we sought to understand whether G_αt1 translocation might also play a role in synaptic transmission and affect rod bipolar cell sensitivity.

Methods: : We generated a transgenic mouse with impaired G_αt1 translocation by replacing the native G_αt1 with a G_αt1A3C (A3C⁺) mutant that is more tightly associated with membranes due to N-acylation and S-palmitoylation. G_αt1^+/- mice, which express similar G_αt concentration to A3C⁺ mice, were used as controls. We studied the light-evoked flash response of rods using suction electrodes, and rod bipolar cells in retinal slices using patch electrodes under dark-adapted conditions and after light-induced G_αt translocation (light adaptation at 500 lux for 45 min followed by 30 min dark adaptation). Recordings were halted at 1 hour following the light adaptation to ensure that G_αt remained substantially in rod inner segments.

Results: : Following light adaptation, A3C⁺ rods displayed 8-fold increased sensitivity than control rods. In addition, A3C⁺ rods also did not display speeded response kinetics of the dim flash response, compared to control rods that exhibited a speeded time-to-peak. These changes following light adaptation are consistent with a role of G_αt translocation in rod light adaptation. Surprisingly, following light adaptation A3C⁺ rod bipolar cells displayed ~2-fold reduced sensitivity compared to control rod bipolar cells.

Conclusions: : The reduced sensitivity of A3C⁺ rod bipolar cells following light-adaptation, despite more sensitive rod photoresponses (due to impaired G_αt translocation), suggests that G_αt1 translocation facilitates a reduction in glutamate release from rod spherules during the normal light-evoked response. Such sensitization of signal transmission may allow a larger part of the dynamic range of rod bipolar cells to be utilized for enhanced sensitivity under conditions where the rod photocurrent is already light-adapted.

Keywords: retina: distal (photoreceptors, horizontal cells, bipolar cells) • synapse • photoreceptors: visual performance