Light-evoked changes in extracellular pH in frog retina

doi:10.1016/0042-6989(89)90054-0

Vision Research

Volume 29, Issue 9, 1989, Pages 1069-1077

https://doi.org/10.1016/0042-6989(89)90054-0 Get rights and content

Abstract

Light-induced changes in extracellular H⁺ concentration (ΔpH₀) were studied with intraretinal H⁺-sensitive double-barreled microelectrodes in frog eyecup and isolated retina preparations. The most prominent ΔpH₀ were found in the inner plexiform layer, as pH increases (alkalinizations) at light onset and offset. With a small-spot stimulus (0.3 mm dia.), 30 sec in duration, the ΔpH₀ were relatively small (0.03 pH units), and long lasting (peak at 25–30 sec). They were enhanced by flicker (0.3 Hz). Depth profiles paralleled those of the field potentials (PNR/M-wave), the ON ΔpH₀ peaking 40 μm more proximal than the OFF response. The ΔpH₀ exhibited surround antagonism, which was blocked by tetrodotoxin (TTX), indicating an independence from action potentials. The mechanism for these pH increases in proximal retina is not yet understood. In the subretinal space diffuse retinal illumination produced a small pH increase, consistent with a presumed decrease in photoreceptor lactate production. Inhibition of carbonic anhydrase (CA) with acetazolamide or methazolamide increased both the proximal and distal retinal ΔpH₀, suggesting that CA is involved in buffering retinal pH.

Reference (39)

BhattacherjeeP.
Distribution of carbonic anhydrase in the rabbit eye as demonstrated histochemically
Experimental Eye Research
(1971)
EndresW. et al.
Changes in extracellular pH during electrical stimulation of isolated rat vagus nerve
Neuroscience Letters
(1986)
KarwoskiC.J. et al.
Generation of the e-wave of the electroretinogram in frog regina
Vision Research
(1988)
MosconaA.A.
On glutamine synthetase, carbonic anhydrase and Müller glia in the retina
SteinbergR.H. et al.
Retinal pigment epithelial cell contributions to the electroretinogram
TsacopoulosM. et al.
Intraretinal acid-base studies using pH glass microelectrodes: Effects of respiratory and metabolic acidosis and alkalosis on inner-retinal pH
Experimental Eye Research
(1976)
WalzW. et al.
Lactate production and release in cultured astrocytes
Neuroscience Letters
(1988)
AmmannD. et al.
Neutral carrier based hydrogen ion selective microelectrode for extra and intracellular studies
Analytical Chemistry
(1981)
BalestrinoM. et al.
Concentration of carbon dioxide, interstitial pH and synaptic transmission in hippocampal formation of the rat
Journal of Physiology, London
(1988)
BorgulaG.A. et al.
Light-evoked changes of [H⁺]₀ in the retina of the intact cut eye

BorgulaG.A. et al.

Light-evoked pH changes in the retina of the in vitro frog eyecup

BurkhardtD.A.

Proximal negative response of frog retina

Journal of Neurophysiology

(1970)

BykovK.A. et al.

Light-induced efflux of calcium ions from cones of the retina

Report of the Academy of Sciences of the USSR

(1985)

CarliniW.G. et al.

Regional variation in stimulated extracellular pH transients in the mammalian CNS

Neuroscience Abstracts

(1986)

DeitmerJ.W. et al.

The regulation of intracellular pH by identified glial cells and neurones in the central nervous system of the leech

Journal of Physiology, London

(1987)

GoldG.H. et al.

Light-induced Ca release by intact retinal rods

GovardovskiV.I. et al.

Light-induced calcium release from retinal photoreceptors and the “calcium hypothesis” of visual excitation

Biological Membranes

(1987)

HansenA.J.

Effect of anoxia on ion distribution in the brain

Physiological Reviews

(1985)

KaoC.Y.

Tetrodotoxin, saxitoxin and there significance in the study of excitation phenomenona

Pharmacological Reviews

(1966)

Cited by (79)

Circadian clock organization in the retina: From clock components to rod and cone pathways and visual function
2023, Progress in Retinal and Eye Research
Citation Excerpt :
In the retina, the pH of the extracellular space varies with light stimulation and light/dark adaptation. Light stimulation produces an alkalinization of the extracellular space that surrounds photoreceptor cells (Borgula et al., 1989; Oakley and Wen, 1989; Yamamoto et al., 1992). Conversely, dark adaptation produces an acidification.
Circadian (24-h) clocks are cell-autonomous biological oscillators that orchestrate many aspects of our physiology on a daily basis. Numerous circadian rhythms in mammalian and non-mammalian retinas have been observed and the presence of an endogenous circadian clock has been demonstrated. However, how the clock and associated rhythms assemble into pathways that support and control retina function remains largely unknown. Our goal here is to review the current status of our knowledge and evaluate recent advances. We describe many previously-observed retinal rhythms, including circadian rhythms of morphology, biochemistry, physiology, and gene expression. We evaluate evidence concerning the location and molecular machinery of the retinal circadian clock, as well as consider findings that suggest the presence of multiple clocks. Our primary focus though is to describe in depth circadian rhythms in the light responses of retinal neurons with an emphasis on clock control of rod and cone pathways. We examine evidence that specific biochemical mechanisms produce these daily light response changes. We also discuss evidence for the presence of multiple circadian retinal pathways involving rhythms in neurotransmitter activity, transmitter receptors, metabolism, and pH. We focus on distinct actions of two dopamine receptor systems in the outer retina, a dopamine D₄ receptor system that mediates circadian control of rod/cone gap junction coupling and a dopamine D₁ receptor system that mediates non-circadian, light/dark adaptive regulation of gap junction coupling between horizontal cells. Finally, we evaluate the role of circadian rhythmicity in retinal degeneration and suggest future directions for the field of retinal circadian biology.
Photoreceptors in a mouse model of Leigh syndrome are capable of normal light-evoked signaling
2019, Journal of Biological Chemistry
Citation Excerpt :
Although not directly tested, reduced efflux of lactic acid would be predicted to result in acidification of the interphotoreceptor matrix. Similarly, carbonic anhydrase has been shown to buffer the pH of the interphotoreceptor matrix, with its inhibition resulting in acidification of this compartment (23). Interphotoreceptor matrix acidification might explain the abnormal in vivo ERG responses in both mutations, as low pH is known to decrease the activity of the rod outer segment Na+/Ca2+/K+ exchanger NCKX1 (24), which maintains Ca2+ homeostasis in the outer segment and is critical in supporting normal rod sensitivity and response amplitude (25).
Mitochondrial dysfunction is an important cause of heritable vision loss. Mutations affecting mitochondrial bioenergetics may lead to isolated vision loss or life-threatening systemic disease, depending on a mutation’s severity. Primary optic nerve atrophy resulting from death of retinal ganglion cells is the most prominent ocular manifestation of mitochondrial disease. However, dysfunction of other retinal cell types has also been described, sometimes leading to a loss of photoreceptors and retinal pigment epithelium that manifests clinically as pigmentary retinopathy. A popular mouse model of mitochondrial disease that lacks NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4), a subunit of mitochondrial complex I, phenocopies many traits of the human disease Leigh syndrome, including the development of optic atrophy. It has also been reported that ndufs4^−/− mice display diminished light responses at the level of photoreceptors or bipolar cells. By conducting electroretinography (ERG) recordings in live ndufs4^−/− mice, we now demonstrate that this defect occurs at the level of retinal photoreceptors. We found that this deficit does not arise from retinal developmental anomalies, photoreceptor degeneration, or impaired regeneration of visual pigment. Strikingly, the impairment of ndufs4^−/− photoreceptor function was not observed in ex vivo ERG recordings from isolated retinas, indicating that photoreceptors with complex I deficiency are intrinsically capable of normal signaling. The difference in electrophysiological phenotypes in vivo and ex vivo suggests that the energy deprivation associated with severe mitochondrial impairment in the outer retina renders ndufs4^−/− photoreceptors unable to maintain the homeostatic conditions required to operate at their normal capacity.
Light-induced pH changes in the intact retinae of normal and early diabetic rats
2016, Experimental Eye Research
Double-barreled H⁺-selective microelectrodes were used to measure local extracellular concentration of H⁺ ([H⁺]_o) in the retina of dark-adapted anesthetized Long-Evans rats. The microelectrode advanced in steps of 30 μm throughout the retina from the vitreal surface to retinal pigment epithelium and then to the choroid, recording changes in [H⁺]_o evoked by light stimulation. Recordings were performed in diabetic rats 1–3 months after intraperitoneal injection of streptozotocin and the results were compared with data obtained in age-matched control animals. Brief light stimulation (2.5 s) evoked changes of [H⁺]_o with amplitudes of a few nM. Throughout the retina, there was a transient initial acidification for ∼200 ms followed by steady alkalinization, although amplitudes and kinetics of these components were slightly variable in different retinal layers. No significant difference was found when the light-induced [H⁺]_o changes recorded in various retinal layers of early diabetic rats were compared with the [H⁺]_o changes from corresponding layers of control animals. Also, when H⁺-selective microelectrodes were located in the retinal pigment epithelium (RPE) layer, an increase in H⁺ was recorded, whose time course and amplitude were similar in control and diabetic rats. However, a striking difference between light-induced [H⁺]_o changes in controls and diabetics was observed in the choriocapillaris, in the thin layer (10–20 μm) distal to the basal membrane of the RPE. In control rats, choroidal [H⁺]_o decreased in a few cases, but much more often practically did not change. In contrast, diabetic rats demonstrated either an increase (in half of the cases) or no change in choroidal [H⁺]_o. The data suggest that the active participation of the choroidal blood supply in stabilization of [H⁺]_o could be partially compromised already at early stages of diabetes in rats. Interestingly, it appeared that the acid removal by the choroidal circulation was compromised most after 1 month of diabetes and tended to improve later.
Chloroquine impairs visual transduction via modulation of acid sensing ion channel 1a
2014, Toxicology Letters
Citation Excerpt :
The pH gradient, present in the retina, fluctuates in conjunction with the circadian rhythm. Extracellular protons are shifted by light (Borgula et al., 1989; Yamamoto et al., 1992) and influence the activity and phototransduction of the retina (Brockway et al., 2005; Dmitriev and Mangel, 2001; Ettaiche et al., 2006; Ettaiche et al., 2004; Lilley et al., 2004; Maubaret et al., 2002). ASICs, which are extracellular pH sensors activated by protons, participate in the transduction of visual signals (Ettaiche et al., 2006; Ettaiche et al., 2009; Ettaiche et al., 2004).
Acid-sensing ion channels (ASICs) are extracellular pH sensors activated by protons, which influence retinal activity and phototransduction. Among all ASICs, ASIC1a is abundantly expressed in the retina and involved in normal retinal activity. Chloroquine, which has been used in the treatment of malaria, rheumatoid arthritis and systemic lupus erythematosus, has been shown to be toxic to the retina. However, the underlying mechanisms remain unclear. In this study, we investigated the role of chloroquine in phototransduction by measuring the electroretinogram (ERG). The effect of chloroquine on acid-evoked currents in either isolated rat retinal ganglion neurons (RGNs) or Chinese hamster ovary (CHO) cells transfected with ASIC1a were assessed using a whole-cell patch-clamp technique. Chloroquine reduced the b-wave of scotopic 0.01 and photopic 3.0 and amplitudes of oscillatory potentials (OPs), an effect which was almost completely reversed by PcTx1, an ASIC1a-specific channel blocker. Further, patch-clamp experiments demonstrated that chloroquine reduced the peak current amplitude and prolonged the activation and desensitization of ASIC1a currents. These chloroquine-induced effects on the kinetics of ASIC 1a were dose-, pH- and Ca²⁺-dependent. Taken together, these results demonstrate that chloroquine affects vision conduction by directly modifying the kinetics of ASIC1a. Such a mechanism, may, in part, explain the retinal toxicity of chloroquine.
Cell Biology of the Müller Cell
2012, Retina Fifth Edition
Lateral interactions in the outer retina
2012, Progress in Retinal and Eye Research
Citation Excerpt :
Blocking pH changes with HEPES would diminish such a change in ephaptic current and could thus reduce feedback effects at the cone pedicle. Although enhanced pH buffering has been consistently shown to block horizontal cell to cone feedback, a difficulty with a proton-mediated mechanism of horizontal cell feedback to cones is that measurements of extracellular pH made using H+-selective microelectrodes have found that light stimulation alters the extracellular pH of the outer retina of frogs, fish, rabbits and cats by only ∼0.04 pH units (Borgula et al., 1989; Oakley and Wen, 1989; Yamamoto et al., 1992; Dmitriev and Mangel, 2000, 2001). This contrasts with the much larger pH changes predicted by the proton hypothesis.
Lateral interactions in the outer retina, particularly negative feedback from horizontal cells to cones and direct feed-forward input from horizontal cells to bipolar cells, play a number of important roles in early visual processing, such as generating center-surround receptive fields that enhance spatial discrimination. These circuits may also contribute to post-receptoral light adaptation and the generation of color opponency. In this review, we examine the contributions of horizontal cell feedback and feed-forward pathways to early visual processing. We begin by reviewing the properties of bipolar cell receptive fields, especially with respect to modulation of the bipolar receptive field surround by the ambient light level and to the contribution of horizontal cells to the surround. We then review evidence for and against three proposed mechanisms for negative feedback from horizontal cells to cones: 1) GABA release by horizontal cells, 2) ephaptic modulation of the cone pedicle membrane potential generated by currents flowing through hemigap junctions in horizontal cell dendrites, and 3) modulation of cone calcium currents (I_Ca) by changes in synaptic cleft proton levels. We also consider evidence for the presence of direct horizontal cell feed-forward input to bipolar cells and discuss a possible role for GABA at this synapse. We summarize proposed functions of horizontal cell feedback and feed-forward pathways. Finally, we examine the mechanisms and functions of two other forms of lateral interaction in the outer retina: negative feedback from horizontal cells to rods and positive feedback from horizontal cells to cones.

View all citing articles on Scopus

View full text

Light-evoked changes in extracellular pH in frog retina

Abstract

Experimental Eye Research

Neuroscience Letters

Vision Research

Experimental Eye Research

Neuroscience Letters

Neutral carrier based hydrogen ion selective microelectrode for extra and intracellular studies

Analytical Chemistry

Concentration of carbon dioxide, interstitial pH and synaptic transmission in hippocampal formation of the rat

Journal of Physiology, London

Light-evoked changes of [H+]0 in the retina of the intact cut eye

Light-evoked pH changes in the retina of the in vitro frog eyecup

Proximal negative response of frog retina

Journal of Neurophysiology

Light-induced efflux of calcium ions from cones of the retina

Report of the Academy of Sciences of the USSR

Regional variation in stimulated extracellular pH transients in the mammalian CNS

Neuroscience Abstracts

The regulation of intracellular pH by identified glial cells and neurones in the central nervous system of the leech

Journal of Physiology, London

Light-induced Ca release by intact retinal rods

Light-induced calcium release from retinal photoreceptors and the “calcium hypothesis” of visual excitation

Biological Membranes

Effect of anoxia on ion distribution in the brain

Physiological Reviews

Tetrodotoxin, saxitoxin and there significance in the study of excitation phenomenona

Pharmacological Reviews

Light-evoked changes of [H⁺]₀ in the retina of the intact cut eye