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

Abstract

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 (ICa) in the cones, and shifted the activation voltage of ICa to negative voltages. External alkalinization also increased cone ICa and shifted its activation voltage toward negative voltages. Enrichment of the pH buffering capacity of the extracellular solution increased cone ICa, and blocked any additional increase in cone ICa by surround illumination. Hyperpolarization of the HCs by a glutamate receptor antagonist-augmented cone ICa, whereas depolarization of the HCs by kainate suppressed cone ICa. 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.

Synaptic transmission at retinal ribbon synapses

“…The susceptibility of I Ca to changes in pH was established earlier by Barnes and Bui (1991) and Barnes et al (1993). In the newt retina, Hirasawa and Kaneko (2003) found that strong pH buffering largely eliminated the surround-induced shift in the cone I Ca . They postulate that in an intact preparation, the pH of the synaptic cleft is more acidic (by about 0.2 pH unit) than the extracellular pool, and that surround illumination, by hyperpolarizing the horizontal cell, reduces the proton level in the cleft.…”

“…New evidence on this point (Hirasawa and Kaneko, 2003) suggests that pH may play a crucial role. The susceptibility of I Ca to changes in pH was established earlier by Barnes and Bui (1991) and Barnes et al (1993).…”

Calmodulin enhances ribbon replenishment and shapes filtering of synaptic transmission by cone photoreceptors

“…Although we show that I Ca also facilitates in cones, this appears not to be the origin of the Ca 2+ / CaM-dependent recovery process we describe here, as I Ca facilitation is unperturbed by the CaM inhibitors that slow recovery. However, because protons play a key role in regulating photoreceptor I Ca (DeVries 2001; Hirasawa and Kaneko, 2003), a similar mechanism may contribute to recovery from synaptic depression under conditions with reduced extracellular pH buffering, e.g., with a bicarbonate-based saline solution. In hair cells, although synaptic transmission facilitates when resting intracellular [Ca 2+ ] is reduced with a hyperpolarized holding potential, depression dominates at physiological resting potentials .…”

Cellular distribution and subcellular localization of molecular components of vesicular transmitter release in horizontal cells of rabbit retina

“…Finally, no highaffinity transport of [ 3 H] GABA or GABA analogs by horizontal cells has been reported for any adult mammalian retina (Ehinger, 1977;Blanks & Roffler-Tarlov, 1982;Mosinger and Yazulla, 1985;Wä ssle & Chun, 1988Löhrke et al, 1994). More recently, alternative mechanisms of horizontal cell feedback involving electrical resistance or ephaptic feedback onto cones in goldfish (Kamer- Kamermans and Fahrenfort, 2004) and a pH-dependent modulation of cone calcium channels in newts (Hirasawa and Kaneko, 2003) have been proposed. Proton release that occurs with vesicular release may contribute to an increase in proton concentration in the synaptic cleft that produces the shift in the currentvoltage relation of the calcium current (Hirasawa and Kaneko, 2003).…”