Neurotransmitter localization in the skate retina

Bruun, Anitha; Ehinger, Berndt; Sytsma, V.

doi:10.1016/0006-8993(84)90972-7

Cited by 54 publications

(25 citation statements)

References 43 publications

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“…Our findings may appear to be at odds with the results cited earlier, indicating that in skate, uptake of radiolabeled GABA appears to be exclusively in Muller cells (6,7). In (31,32).…”

Section: Discussioncontrasting

confidence: 94%

“…This may give rise to a sodium-dependent release of endogenous GABA and the activation, in turn, of GABA receptors on bipolar cells (9) (there is as yet no evidence of feedback from horizontal cells to skate rods). This hypothesis is consistent with the findings that skate horizontal cells contain both GABA and its synthetic enzyme (4,5) and with the observation that the Muller cells provide an efficient uptake system for the removal of extracellular GABA (6,7). Clearly, the present study was designed to examine only the uptake of GABA.…”

Section: Discussionsupporting

confidence: 88%

“…The results of autoradiographic studies on the cellular localization of exogenously applied [3H]GABA suggest that uptake is almost exclusively within the radial glia (Muller cells) of the skate retina (6,7). However, intracellular recordings obtained both in situ (8) and from isolated cells (9) indicate that skate horizontal cells are depolarized by GABA.…”

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confidence: 99%

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Effects of gamma-aminobutyric acid on skate retinal horizontal cells: evidence for an electrogenic uptake mechanism.

Malchow

Ripps

1990

Proc. Natl. Acad. Sci. U.S.A.

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In the retinae of many vertebrates, there are classes of horizontal cell that probably utilize r-aminobutyric acid (GABA) as a neurotransmitter. As with other amino acid transmitter agents, the postsynaptic action of GABA is thought to be terminated by uptake into neurons and glia surrounding the release site. The present study examined whether an uptake system for GABA could be detected in isolated skate horizontal cells by means of electrophysiological methods. Pressure ejection of GABA onto voltage-clamped horizontal cells produced an inward current that showed no sign of desensitization regardless of the GABA concentration. The dose-response relationship followed simple Michaelis-Menten kinetics, with a half-maximal response elicited at =110 ,AM. Nipecotic acid produced a similar current and reduced the responses to GABA when introduced in the bath solution prior to the GABA pulse.On the other hand, application of 500 ,uM muscimol or 1 mM baclofen, GABAA and GABAB receptor agonists, respectively, were completely without effect. The GABA-induced current was not blocked by superfusion with 500 jAM bicuculline, 500 ,uM picrotoxin, or 500 ,uM phaclofen. However, the responses to GABA were abolished when the cells were superfused in Ringer's solution in which choline or lithium had been substituted for sodium, and were reduced when the extracellular chloride concentration was decreased from 266 mM to 16 mM. Current-voltage data showed a maximal response to GABA when the cells were held at or below their resting potential. At more depolarized levels, the inward current became progressively smaller until, near +50 mV, it could no longer be detected; over the range tested (-90 to +50 mV), the response never reversed into an outward current. These findings suggest that the GABA-induced currents in skate horizontal cells are mediated by an electrogenic uptake mechanism.

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“…Our findings may appear to be at odds with the results cited earlier, indicating that in skate, uptake of radiolabeled GABA appears to be exclusively in Muller cells (6,7). In (31,32).…”

Section: Discussioncontrasting

confidence: 94%

Section: Discussionsupporting

confidence: 88%

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Effects of gamma-aminobutyric acid on skate retinal horizontal cells: evidence for an electrogenic uptake mechanism.

Malchow

Ripps

1990

Proc. Natl. Acad. Sci. U.S.A.

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“…Because skate Muller cells exhibit avid uptake of exogenous GABA (24,25) (26,27). It is generally believed that the b-wave is the extracellular expression of radial current flow generated by a potassium-mediated depolarization of the Muller cells (28)(29)(30) (38,39).…”

Section: Resultsmentioning

confidence: 99%

gamma-Aminobutyric acid (GABA)-induced currents of skate Muller (glial) cells are mediated by neuronal-like GABAA receptors.

Malchow

Qian

Ripps

1989

Proc. Natl. Acad. Sci. U.S.A.

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Radial glia (Muller cells) of the vertebrate retina appear to be intimately involved in regulating the actions of amino acid neurotransmitters. One of the amino acids thought to be important in mediating retinal information flow is y-aminobutyric acid (GABA). The rmdings of this study indicate that enzymatically isolated skate Muller cells are depolarized by GABA and the GABAA agonist muscimol and that the actions of these agents are reduced by bicuculline and picrotoxin. Membrane currents induced by GABA under voltage clamp were dose dependent, were associated with an increase in membrane conductance, and showed marked desensitization when the concentration of GABA exceeded 2.5ImM. The responses had a reversal potential close to that calculated for chloride, indicating that the currents were generated by ions passing through channels. These data support the view that skate Muller cells possess functional GABAA receptors. The presence of such receptors on retinal glia may have important implications for the role of Muller cells in maintaining the constancy of the extracellular milieu, for neuron-glia interactions within the retina, and for theories concerning the generation of the electroretinogram.Glial cells can no longer be thought of as the "silent supporters" of neurons-i.e., electrically inexcitable elements whose passive properties serve to maintain the constancy of the extracellular milieu. Several voltage-sensitive currents have been ascribed to various types of glia throughout the nervous system (1-3), and there is evidence to indicate that the cellular potential of glial cells can be altered by electrogenic uptake mechanisms (4) as well as by ligand-gated ionophores (5). However, depending on the species and type of glial element, there is a striking heterogeneity in the nature of the voltage-dependent channels (6), the cellular responses to neurotransmitters (7,8), and the underlying mechanisms mediating these reactions (9, 10).We report here that a similar heterogeneity is evident in the electrical behavior of the radial glia (Muller cells) of the vertebrate retina, in particular with respect to their responses to the retinal neurotransmitters glutamatq and y-aminobutyric acid (GABA). Brew and Attwell (11) have shown that glutamate evokes a large inward current in isolated voltageclamped Muller cells of axolotl and provide evidence that the current is due to an electrogenic glutamate uptake mechanism activated by intracellular potassium (12). Results of the present study show that skate Muller cells are relatively insensitive to glutamate, whereas GABA induces large current responses that are mediated primarily by a neuronal-like receptor mechanism. MATERIALS AND METHODSCell Dissociation. Skate (Raja erinacea and Raja oscellata) were obtained from the Marine Biological Laboratory (Woods Hole, MA) and maintained for periods of up to 1 month in a tank of circulating artificial seawater held at 14'C; a 12-hr light/dark cycle was used. Prior to enucleation, animals were dark adapted for 1.5 hr, ...

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“…Histological studies and experiments using stimulation of the autonomic system have revealed a rich autonomic vasoactive nerve supply to the choroid (Ehinger, 1966;Ruskell, 1971;Stjernschantz and Bill, 1980, Nilsson et al, 1985, Stone, 1986. Sympathetic innervation includes adrenergic and neuropeptide nerve fibres (Bruun et al, 1984), whereas parasympathetic nerves are primarily cholinergic (Bill and Sperber, 1990). The input from the autonomic nervous system may make a significant contribution to changes in choroidal thickness and regulation of eye growth (Brunstock and Sillito, 1999;Chen et al, 2003;Neuhuber and Schrödl, 2011).…”

Section: The Autonomic Control Of Choroidal Thickness Changesmentioning

confidence: 99%

The Influence of the Autonomic Nervous System on the Human Choroid

Sander¹

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v AbstractThe impact of myopia is greater than just its optical consequences and in severe cases it can lead to a loss of vision. It is a highly prevalent eye disorder, with about one third of the population worldwide affected by this refractive error. Despite extensive research, the pathogenesis of myopia is still only partially understood. An improved knowledge of mechanisms underlying myopia is critical to developing new therapies to prevent myopia or to slow its progression.Although there is no fully effective and satisfactory myopia control treatment available, growing evidence has suggested that the choroid has a passive or active role in the regulation of eye growth and refractive error development. Numerous human and animal studies have shown that the retina can be moved forward or backward towards the image plane through changes in choroidal thickness, and these changes are likely to be associated in the longer term with eye growth and the development of refractive errors. As the choroid receives a rich innervation from the autonomic nervous system, many previous animal studies have utilized pharmacological agents and neurotoxins to elucidate the possible role of muscarinic signaling in the regulation of choroidal thickness, but only a few studies have investigated this issue in humans. An improved understanding of the mechanisms that control choroidal thickness may be important in developing new therapies for combating the development and progression of myopia.The research described in the thesis aimed to investigate the role of the autonomic nervous system in the control of choroidal thickness, axial length and the morphology In a series of experiments, we have confirmed that in humans under normal visual conditions, the parasympathetic nervous system is involved in the short-term regulation of subfoveal and parafoveal choroidal thickness, axial length and the morphology of the anterior sclera. The muscarinic blocker homatropine caused a significant subfoveal and parafoveal choroidal thickening, shortening of axial length, an enlargement of Schlemm's canal area and an increase in thickness of the conjunctival/episcleral complex. On the other hand, no notable changes in ocular parameters, except a decrease in the thickness of the conjunctival/episcleral tissues were found after instillation of the sympathomimetic drug phenylephrine.In an attempt to further improve our understanding of the myopigenic mechanisms influencing the thickness of the choroid in humans, we investigated the short-term influence of mixed interventions (positive and negative lens-imposed defocus / 2% homatropine) on choroidal thickness and axial length in emmetropic and myopic subjects. Homatropine prevented choroidal thinning in response to hyperopic defocus.This finding is consistent with the anti-myopia effects of muscarinic blockers and supports the potential importance of hyperopic defocus in the development of human myopia. By contrast, co-administration of homatropine with myopic defocus did not enhance the thicken...

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Neurotransmitter localization in the skate retina

Cited by 54 publications

References 43 publications

Effects of gamma-aminobutyric acid on skate retinal horizontal cells: evidence for an electrogenic uptake mechanism.

Effects of gamma-aminobutyric acid on skate retinal horizontal cells: evidence for an electrogenic uptake mechanism.

gamma-Aminobutyric acid (GABA)-induced currents of skate Muller (glial) cells are mediated by neuronal-like GABAA receptors.

The Influence of the Autonomic Nervous System on the Human Choroid

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