A Role for Ligand-Gated Ion Channels in Rod Photoreceptor Development

Young, Tracy L.; Cepko, Constance L.

doi:10.1016/s0896-6273(04)00141-2

Cited by 130 publications

(108 citation statements)

References 79 publications

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“…The ρ1-3 subunits were only detected in the postnatal brain and their expression was up-regulated one week after birth. This is consistent with the results from the visual system (Alakuijala et al, 2005;Young and Cepko, 2004). In the lung, ρ1 subunit mRNA was up-regulated at gestational day 19 and at birth (Fig.…”

Section: Summary and Further Discussionsupporting

confidence: 91%

Ionotropic GABA receptor expression in the lung during development

Jin

Guo

Sun

et al. 2008

Gene Expression Patterns

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Cl − transport is essential for lung development. Because gamma-aminobutyric acid (GABA) receptors allow the flow of negatively-charged Cl − ions across the cell membrane, we hypothesized that the expression of ionotropic GABA receptors are regulated in the lungs during development. We identified 17 GABA receptor subunits in the lungs by real-time PCR. These subunits were categorized into 4 groups: Group 1 had high mRNA expression during fetal stages and low in adults; Group 2 had steady expression to adult stages with a slight up-regulation at birth; Group 3 showed an increasing expression from fetal to adult lungs; and Group 4 displayed irregular mRNA fluctuations. The protein levels of selected subunits were also determined by Western blots and some subunits had protein levels that corresponded to mRNA levels. Further studied subunits were primarily localized in epithelial cells in the developing lung with differential mRNA expression between isolated cells and whole lung tissues. Our results add to the knowledge of GABA receptor expression in the lung during development. Keywordslungs; ionotropic GABA receptor; fetal lung development; chloride homeostasis; lung fluid transport; real time PCR; gene expression; alveolar epithelial cells RESULTS AND DISCUSSION SignificanceCl − channels play an important role in the lung throughout an animal's life. During the fetal stages, the lung is a fluid-secreting organ. The main driving force for fluid secretion is the active secretion of Cl − into the developing lungs. Therefore, Cl − channels are indispensable for fetal lung development and morphogenesis (Folkesson et al., 1998;Olver et al., 2004;Bland and Nielson, 1992). On the other hand, the adult lung is air-filled and maintains a "dry" state. The apical surface is covered by a thin layer of alveolar surface fluid. This layer of fluid is required for the proper air exchange and airway defenses. Cl − channels are also essential for maintaining the composition and volume of the alveolar surface fluid (Brochiero et al., 2004 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Several Cl − channels have previously been studied in the lung. The cystic fibrosis transmembrane conductance regulator (CFTR) (Harris et al., 1991), the voltage-gated Cl − channels, ClC2 (Thiemann et al., 1992), ClC3 (Lamb et al., 2001), and ClC5 (Edmonds et al., 2002, and Na + -K + -Cl − cotransporter (NKCC) (Rochelle et al., 2000) have been detected in fetal lungs, distal airway epithelial cells and alveolar epithelial cells. Some of the channels have been shown to be involved in fluid homeostasis i...

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Section: Summary and Further Discussionsupporting

confidence: 91%

Ionotropic GABA receptor expression in the lung during development

Jin

Guo

Sun

et al. 2008

Gene Expression Patterns

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“…However, other amino acids found in the CNS, such as taurine and β-alanine, also gate GlyRs but act as partial agonists (55). GlyR α2-mediated currents in response to taurine have been implicated in the differentiation of cortical and retinal (56) neurons; however, the analysis of Glra2 −/Y mice failed to reveal retinal or cortical abnormalities (54). Notably, the GlyR α subunits expressed in brain respond differently to taurine and β-alanine, such that these amino acids have little to no efficacy at homomeric α2 or α3 GlyRs but do activate α1 GlyRs, albeit with less efficacy and potency than glycine (57,58).…”

Section: Discussionmentioning

confidence: 99%

Glycine receptor α3 and α2 subunits mediate tonic and exogenous agonist-induced currents in forebrain

McCracken

Lowes

Salling

et al. 2017

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

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Neuronal inhibition can occur via synaptic mechanisms or through tonic activation of extrasynaptic receptors. In spinal cord, glycine mediates synaptic inhibition through the activation of heteromeric glycine receptors (GlyRs) composed primarily of α1 and β subunits. Inhibitory GlyRs are also found throughout the brain, where GlyR α2 and α3 subunit expression exceeds that of α1, particularly in forebrain structures, and coassembly of these α subunits with the β subunit appears to occur to a lesser extent than in spinal cord. Here, we analyzed GlyR currents in several regions of the adolescent mouse forebrain (striatum, prefrontal cortex, hippocampus, amygdala, and bed nucleus of the stria terminalis). Our results show ubiquitous expression of GlyRs that mediate large-amplitude currents in response to exogenously applied glycine in these forebrain structures. Additionally, tonic inward currents were also detected, but only in the striatum, hippocampus, and prefrontal cortex (PFC). These tonic currents were sensitive to both strychnine and picrotoxin, indicating that they are mediated by extrasynaptic homomeric GlyRs. Recordings from mice deficient in the GlyR α3 subunit (Glra3 −/− ) revealed a lack of tonic GlyR currents in the striatum and the PFC. In Glra2 −/Y animals, GlyR tonic currents were preserved; however, the amplitudes of current responses to exogenous glycine were significantly reduced. We conclude that functional α2 and α3 GlyRs are present in various regions of the forebrain and that α3 GlyRs specifically participate in tonic inhibition in the striatum and PFC. Our findings suggest roles for glycine in regulating neuronal excitability in the forebrain.glycine receptor | tonic inhibition | Cys-loop receptor | strychnine | alpha subunits

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“…It is possible that the mechanism regulating the exit of interneuron progenitors from the cell cycle relies on glycinergic signaling yet is less dependent on the chloride gradient and the associated excitation, unlike neuronal fate decisions. Supporting this possibility are results from a study on rat retinal progenitors using gain-and loss-of-function GlyR␣2 (Young and Cepko, 2004), which highlighted the role of GlyR␣2 in exit from the cell cycle and differentiation. In that study, the increase in rod progenitor proliferation detected during GlyR␣2 overexpression was abolished when overexpressing channels with impaired ligand binding but was preserved when overexpressing GlyR␣2 with mutated channel gating (Young and Cepko, 2004).…”

Section: Normal Proliferation With Fewer Neuronsmentioning

confidence: 92%

Neurogenic Role of the Depolarizing Chloride Gradient Revealed by Global Overexpression of KCC2 from the Onset of Development

Reynolds¹,

Brustein²,

Liao³

et al. 2008

J. Neurosci.

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GABA-and glycine-induced depolarization is thought to provide important developmental signals, but the role of the underlying chloride gradient has not been examined from the onset of development. We therefore overexpressed globally the potassium-chloride cotransporter 2 (KCC2) in newly fertilized zebrafish embryos to reverse the chloride gradient. This rendered glycine hyperpolarizing in all neurons, tested at the time that motor behaviors (but not native KCC2) first appear. KCC2 overexpression resulted in fewer mature spontaneously active spinal neurons, more immature silent neurons, and disrupted motor activity. We observed fewer motoneurons and interneurons, a reduction in the elaboration of axonal tracts, and smaller brains and spinal cords. However, we observed no increased apoptosis and a normal complement of sensory neurons, glia, and progenitors. These results suggest that chloride-mediated excitation plays a crucial role in promoting neurogenesis from the earliest stages of embryonic development.

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A Role for Ligand-Gated Ion Channels in Rod Photoreceptor Development

Cited by 130 publications

References 79 publications

Ionotropic GABA receptor expression in the lung during development

Ionotropic GABA receptor expression in the lung during development

Glycine receptor α3 and α2 subunits mediate tonic and exogenous agonist-induced currents in forebrain

Neurogenic Role of the Depolarizing Chloride Gradient Revealed by Global Overexpression of KCC2 from the Onset of Development

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