GABA and glycine channels in isolated ganglion cells from the goldfish retina.

Cohen, Bruce; Fain, Gordon; Fain, Mindy

doi:10.1113/jphysiol.1989.sp017828

Cited by 38 publications

(28 citation statements)

References 39 publications

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“…GLY (100-200 pM) produced inward, desensitizing currents in every parasol and midget cell tested at a holding potential of -70 mV. The pharmacology and ionic selectivity of GLY receptors on midget and parasol cells were similar to those reported in other retinal neurons (31)(32)(33)(34). For example, strychnine (2-4 ,uM) reversibly blocked the responses to 100 pM GLY by 68% ± 16% (mean ± SD, n = 5) (Fig.…”

Section: Identification Of Midget and Parasol Cells In Primate Retinalsupporting

confidence: 71%

Amino acid receptors of midget and parasol ganglion cells in primate retina.

Zhou

Marshak

Fain

1994

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

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Primate retinas contain two major gaion cell types. Midget (or P One explanation for the differences in the light-response properties of parasol and midget cells is that they are caused by differences in the balance of synaptic input from glutamatergic bipolar cells and GABAergic and GLYergic amacrine cells, or by the properties of the excitatory and inhibitory synaptic receptors on the ganglion cells. We have tested this notion with whole-cell patch-clamp recordings (19) from ganglion cells in a primate retinal-slice preparation. Our results show that the populations of amino acid receptors on midget and parasol cells are remarkably similar and suggest that many differences in the response properties ofthese cells are due, instead, to differences in the types of presynaptic neurons providing input to the ganglion cells.Visual perception in primates is mediated by two parallel pathways, named parvocellular (or P) and magnocellular (or M) for the layers in the lateral geniculate nucleus with which they are associated (1, 2). The major retinal projection to the parvocellular layers is from midget ganglion cells, which comprise 480% of the ganglion cells in the macaque retina (3-5). The midget ganglion cells have small perikarya and dendritic trees (6, 7) that branch in either the distal half ofthe inner plexiform layer (IPL) (sublamina a) or the proximal half (sublamina b) and are named type a or b accordingly. Midget ganglion cells (P cells) have relatively sustained responses to light, which can be either depolarizing or hyperpolarizing, depending on the stimulus wavelength (8). In the central retina, each midget ganglion cell receives approximately half of its input from a single cone (7, 9, 10) via a single, midget bipolar cell (11), and the neurotransmitter at these synapses is thought to be glutamate. The other input to midget ganglion cells is from amacrine cells, most of which use either Y-aminobutyric acid (GABA) or glycine (GLY) as neurotransmitters (12-15). MATERIALS AND METHODSRetinas were obtained from seven adult macaques (Macaca fascicularis) and one adult baboon (Papio Cynocephalus). Animals were sacrificed by other investigators with an overdose ofpentobarbital, and eyes were enucleated within 15 min of death. Retinal slices, typically from midperipheral retina, were prepared as described (20), with modifications to ensure the health of mammalian tissue (21). Eyes were first hemisected, and the vitreous body was removed. A 3-to 5-mmwide strip ofeyecup was cut and placed on nitrocellulose filter paper with the ganglion cell layer ofthe retina facing the paper. The sclera, choroid, and pigment epithelium were then removed, leaving the retina adhering to the filter paper.

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Section: Identification Of Midget and Parasol Cells In Primate Retinalsupporting

confidence: 71%

Amino acid receptors of midget and parasol ganglion cells in primate retina.

Zhou

Marshak

Fain

1994

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

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“…It is likely that retinal neurons express glycine receptors containing ␤ subunits. The main conductance of glycine channels in goldfish ganglion cells is ϳ16 pS (Cohen et al 1989), far below the ϳ80 pS expected in GlyRs made exclusively from alpha subunits. The presence of ␤ subunits makes the potency of picrotoxinin in retina, relative to alpha homomeric receptors, even more unexpected (Pribilla et al 1992).…”

Section: Comparison Of Antagonists In Native and Heterologously Exprementioning

confidence: 74%

“…Yet many studies have shown that picrotoxin is not particularly selective and may act to block glycine receptors (Pribilla et al 1992;Shan et al 2001). There are also reports that SR95531 and bicuculline can inhibit glycine receptors (Cohen et al 1989;Dieudonne 1995;Sun and Machu 2000). We therefore wanted to test these antagonists at commonly employed concentrations to determine their utility in separating GABA and glycine neural circuits in retina.…”

Section: Introductionmentioning

confidence: 99%

Effects of GABA Receptor Antagonists on Retinal Glycine Receptors and on Homomeric Glycine Receptor Alpha Subunits

Wang¹,

Slaughter²

2005

Journal of Neurophysiology

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Wang, Peiyuan and Malcolm M. Slaughter. Effects of GABA receptor antagonists on retinal glycine receptors and on homomeric glycine receptor alpha subunits. J Neurophysiol 93: 3120 -3126, 2005; doi:10.1152/jn.01228.2004. Glycinergic and GABAergic inhibition are juxtaposed at one retinal synaptic layer yet likely perform different functions. These functions have usually been evaluated using receptor antagonists. In examining retinal glycine receptors, we were surprised to find that commonly used concentrations of GABA antagonists blocked significant fractions of the glycine current. In retinal amacrine and ganglion cells, the competitive GABA A receptor antagonists (bicuculline and SR95531) were also competitive GlyR antagonists. Picrotoxinin produced a noncompetitive inhibition of retinal GlyRs. [1,2,5,6-tetrahydropyridine-4-yl] methylphosphinic acid, the GABA C R antagonist, did not inhibit glycine receptors. All three GABA A receptor antagonists were competitive inhibitors of homomeric ␣1 or ␣2 GlyRs expressed in human embryonic kidney cells (HEK293) cells. Interestingly, bicuculline was much more effective at ␣2 GlyRs and might be used to separate glycine receptor subtypes. Thus commonly used concentrations of GABA antagonists do not unambiguously differentiate GABA and glycine pathways. Picrotoxinin inhibition of GABA C receptors requires two amino acids in the second transmembrane region (TM2): 2Ј serine and 6Ј threonine. Although TM2 regions in GABA and glycine receptors are highly homologous, neither 2Ј serine nor 6Ј threonine is essential for picrotoxinin sensitivity in glycine receptors.

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“…To increase the likelihood of a thorough space clamp and dialysis of the cytoplasm against the patch electrode solution (see below), cells were used only if they were neurite-free-namely, usually within 12 hr after cells were dissociated (16). All recordings described here are from somata identified as those of ganglion cells by morphological criteria (5,7).…”

Section: Methodsmentioning

confidence: 99%

(-)-baclofen and gamma-aminobutyric acid inhibit calcium currents in isolated retinal ganglion cells.

Bindokas

Ishida

1991

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

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Of the various synaptic inputs known to converge upon retinal ganglion cells, the major inhibitory inputs are thought to be GABAergic. Although y-aminobutyric acid (GABA) is known to activate anion-selective ion channels in retinal ganglion cells, we have tested the possibility that GABA can also modulate cationic conductances in these cells, as seen in other central and peripheral neurons. Specifically, we have made whole-cell patch-clamp recordings to test whether voltage-gated calcium currents in isolated goldfish retinal ganglion cells are sensitive to GABAB receptor ligands. (-)-Baclofen and GABA inhibited calcium currents activated by moderately long depolarizations and, during large depolarizations (e.g., to 0 mV), also appeared to accelerate the rate of current decay. The calcium current inhibition induced by (-)-baclofen and GABA was not prevented by 2-hydroxysaclofen, phadofen, or bicuculline, even though bicuculline suppressed a GABA-activated conductance in these cells. These results demonstrate the presence of baclofen-and GABAsensitive calcium currents in vertebrate retinal ganglion cells as well as the coexistence of GABAA and GABAB receptors in individual retinal ganglion cells.The inner plexiform layer of the retina is one of the most widely studied synaptic neuropils of vertebrate central nervous system. Here, retinal ganglion cells receive excitatory and inhibitory synaptic inputs from a variety of interneurons known as bipolar and amacrine cells (see ref. 1). Of these inputs, the major inhibitory pathways appear to be GABAergic: endogenous y-aminobutyric acid (GABA), its synthetic enzyme glutamic acid decarboxylase, GABA-sequestering neuronal processes, GABAA receptor-channel complexes, and both muscimol-and benzodiazepine-binding sites are distributed throughout this plexus; GABA and glutamic acid decarboxylase have been localized in amacrine cells forming morphological synapses onto ganglion cells; and many if not all retinal ganglion cells are inhibited by exogenous GABA in various species (2-4).GABA can activate a chloride conductance in both nonmammalian and mammalian retinal ganglion cells (e.g., refs. 5-7). This may not account for all effects of GABA on these cells, however, given observations in other individual central and peripheral neurons that GABA can activate more than one type of receptor (e.g., refs. 8 and 9). The most wellknown of these are GABAB receptors, which are coupled to calcium and potassium conductances and are pharmacologically distinguishable from GABAA receptors coupled to chloride conductances (10). Recent voltage-clamp studies have shown that GABA and the GABAB receptor agonist, baclofen, inhibit calcium currents of retinal cone and bipolar cells (11, 12), while a baclofen-sensitive potassium current has been inferred on the basis of voltage recordings from proximal retinal neurons in situ (13).GABAergic modulation of calcium currents in retinal ganglion cells has not previously been demonstrated to our knowledge. However, because most (if not all) clas...

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GABA and glycine channels in isolated ganglion cells from the goldfish retina.

Cited by 38 publications

References 39 publications

Amino acid receptors of midget and parasol ganglion cells in primate retina.

Amino acid receptors of midget and parasol ganglion cells in primate retina.

Effects of GABA Receptor Antagonists on Retinal Glycine Receptors and on Homomeric Glycine Receptor Alpha Subunits

(-)-baclofen and gamma-aminobutyric acid inhibit calcium currents in isolated retinal ganglion cells.

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