pH Changes in the Invaginating Synaptic Cleft Mediate Feedback from Horizontal Cells to Cone Photoreceptors by Modulating Ca²⁺ Channels

Feedback from horizontal cells (HCs) to cone photoreceptors plays a key role in the center-surround–receptive field organization of retinal neurons. Recordings from cone photoreceptors in newt retinal slices were obtained by the whole-cell patch-clamp technique, using a superfusate containing a GABA antagonist (100 μM picrotoxin). Surround illumination of the receptive field increased the voltage-dependent calcium current (I_Ca) in the cones, and shifted the activation voltage of I_Ca to negative voltages. External alkalinization also increased cone I_Ca and shifted its activation voltage toward negative voltages. Enrichment of the pH buffering capacity of the extracellular solution increased cone I_Ca, and blocked any additional increase in cone I_Ca by surround illumination. Hyperpolarization of the HCs by a glutamate receptor antagonist-augmented cone I_Ca, whereas depolarization of the HCs by kainate suppressed cone I_Ca. From these results, we propose the hypothesis that pH changes in the synaptic clefts, which are intimately related to the membrane voltage of the HCs, mediate the feedback from the HCs to cone photoreceptors. The feedback mediated by pH changes in the synaptic cleft may serve as an additional mechanism for the center-surround organization of the receptive field in the outer retina.