scholarly journals Ih Without Kir in Adult Rat Retinal Ganglion Cells

2007 ◽  
Vol 97 (5) ◽  
pp. 3790-3799 ◽  
Author(s):  
Sherwin C. Lee ◽  
Andrew T. Ishida

Antisera directed against hyperpolarization-activated mixed-cation (“ Ih”) and K+ (“Kir”) channels bind to some somata in the ganglion cell layer of rat and rabbit retina. Additionally, the termination of hyperpolarizing current injections can trigger spikes in some cat retinal ganglion cells, suggesting a rebound depolarization arising from activation of Ih. However, patch-clamp studies showed that rat ganglion cells lack inward rectification or present an inwardly rectifying K+ current. We therefore tested whether hyperpolarization activates Ih in dissociated, adult rat retinal ganglion cell somata. We report here that, although we found no inward rectification in some cells, and a Kir-like current in a few cells, hyperpolarization activated Ih in roughly 75% of the cells we recorded from in voltage clamp. We show that this current is blocked by Cs+ or ZD7288 and only slightly reduced by Ba2+, that the current amplitude and reversal potential are sensitive to extracellular Na+ and K+, and that we found no evidence of Kir in cells presenting Ih. In current clamp, injecting hyperpolarizing current induced a slowly relaxing membrane hyperpolarization that rebounded to a few action potentials when the hyperpolarizing current was stopped; both the membrane potential relaxation and rebound spikes were blocked by ZD7288. These results provide the first measurement of Ih in mammalian retinal ganglion cells and indicate that the ion channels of rat retinal ganglion cells may vary in ways not expected from previous voltage and current recordings.

2000 ◽  
Vol 17 (4) ◽  
pp. 647-655 ◽  
Author(s):  
MASAYASU YOSHIKAWA ◽  
KAJ ANDERSON ◽  
HIRONOBU SAKAGUCHI ◽  
JOHN G. FLANNERY ◽  
PAUL G. FITZGERALD ◽  
...  

Although single-channel and whole-cell patch-clamp recordings have demonstrated the presence of Na+ currents in retinal ganglion cell somata, it has not previously been reported that an anti-Na+-channel antiserum stains both retinal ganglion cell somata and proteins with molecular weights corresponding to complexes of α and β subunits. We probed adult goldfish retinas for Na+ channel-like immunoreactivity with a polyclonal antibody directed against the EOIII segment of vertebrate voltage-gated Na+ channels. In vertical sections and whole mounts, this antibody consistently stained the somata, axons, and proximal dendrites of retinal ganglion cells. Some somata in the proximal third of the inner nuclear layer were also stained. In Western blots, this antibody specifically stained multiple protein bands from retina and optic nerve, all with apparent molecular weights between 200 and 315 kDa. The largest of these molecular weights agrees with that reported previously for complexes of α and β subunits in mammalian neurons, including retinal ganglion cells. The intermediate and lowest molecular weights are consistent with the presence of multiple Na+ channel α subunits, either in individual proximal retinal neurons or in different morphological subtypes.


1991 ◽  
Vol 65 (4) ◽  
pp. 968-979 ◽  
Author(s):  
A. T. Ishida ◽  
V. P. Bindokas ◽  
R. Nuccitelli

1. We have estimated free, intracellular calcium ion concentrations ([Ca]i) in isolated retinal ganglion cells of adult goldfish by ratio-imaging fura-2 emission intensity at two excitation wavelengths. Here we describe [Ca]i in these cells, both at rest and during depolarization by elevated levels of extracellular potassium ions ([K]o). 2. [K]o was varied between 5 and 60 mM in sodium-free, tetrodotoxin-containing salines. Ganglion cell membrane potential, measured with patch electrodes, fell with each increment of [K]o used, from approximately -70 mV in 5 mM K+ to approximately -20 mV in 60 mM K+. 3. In control saline, [Ca]i was roughly 120 nM in cell somata and at least twofold higher in their growth cones. [Ca]i increased in both somata and growth cones to as high as 1.5 microM in salines containing 60 mM K+. [Ca]i exceeded 1.5 microM in some cells in high-K+ salines, although these levels could not be quantified accurately with fura-2. 4. Increases in [Ca]i elicited by elevated [K]o persisted for the duration of the exposure to high-K+ saline and were blocked by replacement of most of the bath Ca2+ by Co2+. These increases in [Ca]i were also sensitive to dihydropyridine calcium-channel ligands, viz., enhanced by BAY K 8644 (3 microM) and antagonized by nifedipine (10 microM). 5. Partial recovery of control [Ca]i occurred when [K]o was reduced to 5 mM after exposure to high-K+ saline and in high-K+ saline when nifedipine was included. These results show that goldfish retinal ganglion cells can partially buffer intracellular Ca2+ in the absence of extracellular Na+ ions. 6. These results provide measurements of the changes in [Ca]i brought about by depolarization of goldfish retinal ganglion cells in Na(+)-free salines. In these salines, at least part of the increase in [Ca]i appears to result from Ca2+ influx through a voltage-activated, noninactivating calcium conductance in the somata and growth cones of these cells. These measurements complement whole-cell patch-clamp and vibrating microprobe recordings from the somata and neurites of these cells and also immunocytochemical studies and patch-clamp measurements in amphibian, reptilian, and mammalian retinal ganglion cells.


1988 ◽  
Vol 60 (2) ◽  
pp. 381-396 ◽  
Author(s):  
A. T. Ishida ◽  
B. N. Cohen

1. We have begun to analyze neurotransmitter-activated conductances in retinal ganglion cells by measuring the response of single voltage-clamped adult goldfish ganglion cells to gamma-aminobutyric acid (GABA). Here we describe 1) our method of identifying ganglion cells in vitro after their dissociation from papain-treated retinas, and 2) the response of these cells to GABA in the tight-seal whole cell configuration of the patch-clamp method (cf. 41) after 1-4 days of primary cell culture. 2. Ganglion cell somata were backfilled in situ by injections of horseradish peroxidase (HRP) into the optic nerve. After dissociation of the retinas containing these cells, HRP reaction product was localized to cells that retained the size, shape, and an intracellular organelle characteristic of ganglion cells in situ. These features enabled us thereafter to identify ganglion cells in vitro without retrograde marker transport. 3. GABA (3-10 microM) elicited inward currents and substantial noise increases in almost all ganglion cells at negative holding potentials. Reversal potential measurements in salines containing different chloride concentrations indicated that GABA produces a chloride-selective conductance increase in ganglion cells. Bicuculline (10 microM) reversibly inhibited ganglion cell GABA responses. Baclofen (10 microM) alone elicited no responses in ganglion cells. 4. Noise analysis of GABA-activated whole cell currents yielded elementary conductance estimates of 16 pS, with a slow time constant of 30 ms plus a faster component of 1-2 ms. No significant voltage dependence of these values was observed between -20 and -80 mV. 5. We have thus devised a means of identifying ganglion cells dissociated from adult retinas, identified GABAA receptors (cf. 16) on these cells, and found that the responses mediated by these receptors resemble those found in other regions of central nervous system (CNS). These results are consistent with the notion that GABA may function as an inhibitory transmitter at synapses on ganglion cells.


2013 ◽  
Vol 6 (1) ◽  
pp. 015001 ◽  
Author(s):  
Barbara Lorber ◽  
Wen-Kai Hsiao ◽  
Ian M Hutchings ◽  
Keith R Martin

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuhong Fu ◽  
Ying Wang ◽  
Xinyuan Gao ◽  
Huiyao Li ◽  
Yue Yuan

Background. Diabetic retinopathy (DR) is a severe complication of diabetes mellitus. DR is considered as a neurovascular disease. Retinal ganglion cell (RGC) loss plays an important role in the vision function disorder of diabetic patients. Histone deacetylase3 (HDAC3) is closely related to injury repair and nerve regeneration. The correlation between HDAC3 and retinal ganglion cells in diabetic retinopathy is still unclear yet. Methods. To investigate the chronological sequence of the abnormalities of retinal ganglion cells in diabetic retinopathy, we choose 15 male db/db mice (aged 8 weeks, 12 weeks, 16 weeks, 18 weeks, and 25 weeks; each group had 3 mice) as diabetic groups and 3 male db/m mice (aged 8 weeks) as the control group. In this study, we examined the morphological and immunohistochemical changes of HDAC3, Caspase3, and LC3B in a sequential manner by characterizing the process of retinal ganglion cell variation. Results. Blood glucose levels and body weights of db/db mice were significantly higher than that of the control group, P<0.01. Compared with the control group, the number of retinal ganglion cells decreased with the duration of disease increasing. HDAC3 expression gradually increased in RGCs of db/db mice. Caspase3 expression gradually accelerated in RGCs of db/db mice. LC3B expression dynamically changed in RGCs of db/db mice. HDAC3 was positively correlated with Caspase3 expression (r=0.7424), P<0.01. HDAC3 was positively correlated with LC3B expression (r=0.7336), P<0.01. Discussion. We clarified the dynamic expression changes of HDAC3, Caspase3, and LC3B in retinal ganglion cells of db/db mice. Our results suggest the HDAC3 expression has a positive correlation with apoptosis and autophagy.


2011 ◽  
Vol 28 (5) ◽  
pp. 403-417 ◽  
Author(s):  
WALTER F. HEINE ◽  
CHRISTOPHER L. PASSAGLIA

AbstractThe rat is a popular animal model for vision research, yet there is little quantitative information about the physiological properties of the cells that provide its brain with visual input, the retinal ganglion cells. It is not clear whether rats even possess the full complement of ganglion cell types found in other mammals. Since such information is important for evaluating rodent models of visual disease and elucidating the function of homologous and heterologous cells in different animals, we recorded from rat ganglion cells in vivo and systematically measured their spatial receptive field (RF) properties using spot, annulus, and grating patterns. Most of the recorded cells bore likeness to cat X and Y cells, exhibiting brisk responses, center-surround RFs, and linear or nonlinear spatial summation. The others resembled various types of mammalian W cell, including local-edge-detector cells, suppressed-by-contrast cells, and an unusual type with an ON–OFF surround. They generally exhibited sluggish responses, larger RFs, and lower responsiveness. The peak responsivity of brisk-nonlinear (Y-type) cells was around twice that of brisk-linear (X-type) cells and several fold that of sluggish cells. The RF size of brisk-linear and brisk-nonlinear cells was indistinguishable, with average center and surround diameters of 5.6 ± 1.3 and 26.4 ± 11.3 deg, respectively. In contrast, the center diameter of recorded sluggish cells averaged 12.8 ± 7.9 deg. The homogeneous RF size of rat brisk cells is unlike that of cat X and Y cells, and its implication regarding the putative roles of these two ganglion cell types in visual signaling is discussed.


Development ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 77-92
Author(s):  
S. C. Sharma ◽  
J. G. Hollyfield

The specification of central connexions of retinal ganglion cells was studied in Xenopus laevis. In one series of experiments, the right eye primordium was rotated 180° at embryonic stages 24–32. In the other series, the left eye was transplanted into the right orbit, and vice versa, with either 0° or 180° rotation. After metamorphosis the visual projections from the operated eye to the contralateral optic tectum were mapped electrophysiologically and compared with the normal retinotectal map. In all cases the visual projection map was rotated through the same angle as was indicated by the position of the choroidal fissure. The left eye exchanged into the right orbit retained its original axes and projected to the contralateral tectum. These results suggest that retinal ganglion cell connexions are specified before stage 24.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michal Geva ◽  
Noga Gershoni-Emek ◽  
Luana Naia ◽  
Philip Ly ◽  
Sandra Mota ◽  
...  

AbstractOptic neuropathies such as glaucoma are characterized by retinal ganglion cell (RGC) degeneration and death. The sigma-1 receptor (S1R) is an attractive target for treating optic neuropathies as it is highly expressed in RGCs, and its absence causes retinal degeneration. Activation of the S1R exerts neuroprotective effects in models of retinal degeneration. Pridopidine is a highly selective and potent S1R agonist in clinical development. We show that pridopidine exerts neuroprotection of retinal ganglion cells in two different rat models of glaucoma. Pridopidine strongly binds melanin, which is highly expressed in the retina. This feature of pridopidine has implications to its ocular distribution, bioavailability, and effective dose. Mitochondria dysfunction is a key contributor to retinal ganglion cell degeneration. Pridopidine rescues mitochondrial function via activation of the S1R, providing support for the potential mechanism driving its neuroprotective effect in retinal ganglion cells.


1992 ◽  
Vol 9 (3-4) ◽  
pp. 389-398 ◽  
Author(s):  
Luiz R. G. Britto ◽  
Dȃnia E. Hamassaki-Britto

AbstractA small number of enkephalin-like immunoreactive cells were observed in the ganglion cell layer of the pigeon retina. Many of these neurons were identified as ganglion cells, since they were retrogradely labeled after injections of fluorescent latex microspheres in the contralateral optic tectum. These ganglion cells were mainly distributed in the inferior retina, and their soma sizes ranged from 12–26 μm in the largest axis. The enkephalin-containing ganglion cells appear to represent only a very small percentage of the ganglion cells projecting to the optic tectum (less than 0.1%). Two to 7 weeks after removal of the neural retina, there was an almost complete elimination of an enkephalin-like immunoreactive plexus in layer 3 of the contralateral, rostrodorsal optic tectum. These data provide evidence for the existence of a population of enkephalinergic retinal ganglion cells with projections to the optic tectum.


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