Modulation of transmission gain by protons at the photoreceptor output synapse

Synaptic transmission of the light response from photoreceptors to second-order cells of the retina was studied with the whole-cell patch-clamp technique in tiger salamander (Ambystoma tigrinum) retinal slices. Synaptic strength is modulated by extracellular pH in a striking manner: Light-sensitive postsynaptic currents in horizontal and bipolar cells were found to be exponential functions of pH, exhibiting an e-fold increase per 0.23 pH unit over the pH range from 7 to 8. Calcium channel currents in isolated photoreceptors were measured and also exhibited proton sensitivity. External alkalinization from pH 7 to 8 shifted the voltage dependence of channel activation negative by 12 mV. A model of the synaptic transfer function suggested that presynaptic Ca channels could be the primary sites of proton action. Increased Ca influx and transmitter release brought about by alkalinization give rise to larger postsynaptic currents. These results suggest that activity-dependent interstitial pH changes known to occur in the retina, while not alleviating signal clipping at this synapse, may provide an adaptative mechanism controlling gain at the photoreceptor output synapse.