scholarly journals Electrophysiology of ionotropic GABA receptors

2021 ◽  
Author(s):  
Erwan Sallard ◽  
Diane Letourneur ◽  
Pascal Legendre
Keyword(s):  
Electrical Activity ◽  
Gaba Receptors ◽  
Chloride Channels ◽  
Expression Patterns ◽  
Cell Types ◽  
Inhibitory Neurotransmitter ◽  
Electrophysiological Properties ◽  
Neuronal Communication ◽  
External Signals ◽  
Brain Gaba

AbstractGABAA receptors are ligand-gated chloride channels and ionotropic receptors of GABA, the main inhibitory neurotransmitter in vertebrates. In this review, we discuss the major and diverse roles GABAA receptors play in the regulation of neuronal communication and the functioning of the brain. GABAA receptors have complex electrophysiological properties that enable them to mediate different types of currents such as phasic and tonic inhibitory currents. Their activity is finely regulated by membrane voltage, phosphorylation and several ions. GABAA receptors are pentameric and are assembled from a diverse set of subunits. They are subdivided into numerous subtypes, which differ widely in expression patterns, distribution and electrical activity. Substantial variations in macroscopic neural behavior can emerge from minor differences in structure and molecular activity between subtypes. Therefore, the diversity of GABAA receptors widens the neuronal repertoire of responses to external signals and contributes to shaping the electrical activity of neurons and other cell types.

scholarly journals Characterization of zebrafish GABAA receptor subunits

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kenichiro Sadamitsu ◽  
Leona Shigemitsu ◽  
Marina Suzuki ◽  
Daishi Ito ◽  
Makoto Kashima ◽  
...  
Keyword(s):  
Gaba Receptors ◽  
Chloride Channels ◽  
Expression Patterns ◽  
Inhibitory Neurotransmitter ◽  
Electrophysiological Properties ◽  
Electrophysiological Recordings ◽  
Physiological Properties ◽  
Spatial Expressions ◽  
The Central Nervous System

Abstractγ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, exerts its effect through the activation of GABA receptors. GABAA receptors are ligand-gated chloride channels composed of five subunit proteins. Mammals have 19 different GABAA receptor subunits (α1–6, β1–3, γ1–3, δ, ε, π, θ, and ρ1–3), the physiological properties of which have been assayed by electrophysiology. However, the evolutionary conservation of the physiological characteristics of diverged GABAA receptor subunits remains unclear. Zebrafish have 23 subunits (α1, α2a, α2b, α3–5, α6a, α6b, β1–4, γ1–3, δ, π, ζ, ρ1, ρ2a, ρ2b, ρ3a, and ρ3b), but the electrophysiological properties of these subunits have not been explored. In this study, we cloned the coding sequences for zebrafish GABAA receptor subunits and investigated their expression patterns in larval zebrafish by whole-mount in situ hybridization. We also performed electrophysiological recordings of GABA-evoked currents from Xenopus oocytes injected with one or multiple zebrafish GABAA receptor subunit cRNAs and calculated the half-maximal effective concentrations (EC50s) for each. Our results revealed the spatial expressions and electrophysiological GABA sensitivities of zebrafish GABAA receptors, suggesting that the properties of GABAA receptor subunits are conserved among vertebrates.

scholarly journals Functional expression of the TMEM16 family of calcium-activated chloride channels in airway smooth muscle

2013 ◽  
Vol 305 (9) ◽  
pp. L625-L634 ◽  
Author(s):  
George Gallos ◽  
Kenneth E. Remy ◽  
Jennifer Danielsson ◽  
Hiromi Funayama ◽  
Xiao Wen Fu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Chloride Channel ◽  
Chloride Channels ◽  
Contractile Function ◽  
Cell Types ◽  
Functional Expression ◽  
Electrophysiological Properties ◽  
New Family ◽  
Electrophysiological Recordings

Airway smooth muscle hyperresponsiveness is a key component in the pathophysiology of asthma. Although calcium-activated chloride channel (CaCC) flux has been described in many cell types, including human airway smooth muscle (HASM), the true molecular identity of the channels responsible for this chloride conductance remains controversial. Recently, a new family of proteins thought to represent the true CaCCs was identified as the TMEM16 family. This led us to question whether members of this family are functionally expressed in native and cultured HASM. We further questioned whether expression of these channels contributes to the contractile function of HASM. We identified the mRNA expression of eight members of the TMEM16 family in HASM cells and show immunohistochemical evidence of TMEM16A in both cultured and native HASM. Functionally, we demonstrate that the classic chloride channel inhibitor, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), inhibited halide flux in cultured HASM cells. Moreover, HASM cells displayed classical electrophysiological properties of CaCCs during whole cell electrophysiological recordings, which were blocked by using an antibody selective for TMEM16A. Furthermore, two distinct TMEM16A antagonists (tannic acid and benzbromarone) impaired a substance P-induced contraction in isolated guinea pig tracheal rings. These findings demonstrate that multiple members of this recently described family of CaCCs are expressed in HASM cells, they display classic electrophysiological properties of CaCCs, and they modulate contractile tone in airway smooth muscle. The TMEM16 family may provide a novel therapeutic target for limiting airway constriction in asthma.

scholarly journals Identifying cell types from single-cell data based on similarities and dissimilarities between cells

2021 ◽  
Vol 22 (S3) ◽  
Author(s):  
Yuanyuan Li ◽  
Ping Luo ◽  
Yi Lu ◽  
Fang-Xiang Wu
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Spectral Clustering ◽  
Incidence Matrix ◽  
Expression Patterns ◽  
Cell Types ◽  
Clustering Method ◽  
Different Types ◽  
Cell Data ◽  
Spectral Clustering Method

Abstract Background With the development of the technology of single-cell sequence, revealing homogeneity and heterogeneity between cells has become a new area of computational systems biology research. However, the clustering of cell types becomes more complex with the mutual penetration between different types of cells and the instability of gene expression. One way of overcoming this problem is to group similar, related single cells together by the means of various clustering analysis methods. Although some methods such as spectral clustering can do well in the identification of cell types, they only consider the similarities between cells and ignore the influence of dissimilarities on clustering results. This methodology may limit the performance of most of the conventional clustering algorithms for the identification of clusters, it needs to develop special methods for high-dimensional sparse categorical data. Results Inspired by the phenomenon that same type cells have similar gene expression patterns, but different types of cells evoke dissimilar gene expression patterns, we improve the existing spectral clustering method for clustering single-cell data that is based on both similarities and dissimilarities between cells. The method first measures the similarity/dissimilarity among cells, then constructs the incidence matrix by fusing similarity matrix with dissimilarity matrix, and, finally, uses the eigenvalues of the incidence matrix to perform dimensionality reduction and employs the K-means algorithm in the low dimensional space to achieve clustering. The proposed improved spectral clustering method is compared with the conventional spectral clustering method in recognizing cell types on several real single-cell RNA-seq datasets. Conclusions In summary, we show that adding intercellular dissimilarity can effectively improve accuracy and achieve robustness and that improved spectral clustering method outperforms the traditional spectral clustering method in grouping cells.

scholarly journals Herbal Remedies and Their Possible Effect on the GABAergic System and Sleep

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 530
Author(s):  
Oliviero Bruni ◽  
Luigi Ferini-Strambi ◽  
Elena Giacomoni ◽  
Paolo Pellegrino
Keyword(s):  
Gaba Receptors ◽  
Herbal Medicines ◽  
Well Being ◽  
Herbal Remedies ◽  
Gamma Aminobutyric Acid ◽  
Systematic Analysis ◽  
Inhibitory Neurotransmitter ◽  
Alternative Medicines ◽  
Molecular Components ◽  
The Brain

Sleep is an essential component of physical and emotional well-being, and lack, or disruption, of sleep due to insomnia is a highly prevalent problem. The interest in complementary and alternative medicines for treating or preventing insomnia has increased recently. Centuries-old herbal treatments, popular for their safety and effectiveness, include valerian, passionflower, lemon balm, lavender, and Californian poppy. These herbal medicines have been shown to reduce sleep latency and increase subjective and objective measures of sleep quality. Research into their molecular components revealed that their sedative and sleep-promoting properties rely on interactions with various neurotransmitter systems in the brain. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that plays a major role in controlling different vigilance states. GABA receptors are the targets of many pharmacological treatments for insomnia, such as benzodiazepines. Here, we perform a systematic analysis of studies assessing the mechanisms of action of various herbal medicines on different subtypes of GABA receptors in the context of sleep control. Currently available evidence suggests that herbal extracts may exert some of their hypnotic and anxiolytic activity through interacting with GABA receptors and modulating GABAergic signaling in the brain, but their mechanism of action in the treatment of insomnia is not completely understood.

Ion channels and G protein-coupled receptors as targets for invertebrate pest control: from past challenges to practical insecticides

2021 ◽  
Author(s):  
Yoshihisa Ozoe
Keyword(s):  
Ion Channels ◽  
G Protein ◽  
Pest Control ◽  
Gaba Receptors ◽  
Chloride Channels ◽  
Structural Changes ◽  
G Protein Coupled Receptors ◽  
Octopamine Receptors ◽  
Sites Of Action ◽  
G Protein Coupled

Abstract In the late 1970s, we discovered that toxic bicyclic phosphates inhibit the generation of miniature inhibitory junction potentials, implying their antagonism of γ-aminobutyric acid (GABA) receptors (GABARs; GABA-gated chloride channels). This unique mode of action provided a strong incentive for our research on GABARs in later years. Furthermore, minor structural changes conferred insect GABAR selectivity to this class of compounds, convincing us of the possibility of GABARs as targets for insecticides. Forty years later, third-generation insecticides acting as allosteric modulator antagonists at a distinctive site of action in insect GABARs were developed. G protein-coupled receptors (GPCRs) are also promising targets for pest control. We characterized phenolamine receptors functionally and pharmacologically. Of the tested receptors, β-adrenergic-like octopamine receptors were revealed to be the most sensitive to the acaricide/insecticide amitraz. Given the presence of multiple sites of action, ion channels and GPCRs remain potential targets for invertebrate pest control.

scholarly journals Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
John A. Halsall ◽  
Simon Andrews ◽  
Felix Krueger ◽  
Charlotte E. Rutledge ◽  
Gabriella Ficz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Histone Modifications ◽  
Expression Patterns ◽  
Cell Types ◽  
Cell Type ◽  
Bar Code ◽  
Genes Encoding ◽  
Cell Type Specific ◽  
Rolling Windows

AbstractChromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear. To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL), to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3. We show that chromosome regions (bands) of 10–50 Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. They comprise 1–5 Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely. We found little change between cell cycle phases, whether compared by 5 Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains. Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription. In conclusion, modified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1 Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses.

scholarly journals Multifaceted Functions of Platelets in Cancer: From Tumorigenesis to Liquid Biopsy Tool and Drug Delivery System

2020 ◽  
Vol 21 (24) ◽  
pp. 9585
Author(s):  
Melania Dovizio ◽  
Patrizia Ballerini ◽  
Rosa Fullone ◽  
Stefania Tacconelli ◽  
Annalisa Contursi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Cells ◽  
Immune Cells ◽  
Expression Patterns ◽  
Cell Communication ◽  
Antiplatelet Agents ◽  
Cell Types ◽  
Disease Monitoring ◽  
Crucial Component ◽  
Numerous Cell

Platelets contribute to several types of cancer through plenty of mechanisms. Upon activation, platelets release many molecules, including growth and angiogenic factors, lipids, and extracellular vesicles, and activate numerous cell types, including vascular and immune cells, fibroblasts, and cancer cells. Hence, platelets are a crucial component of cell–cell communication. In particular, their interaction with cancer cells can enhance their malignancy and facilitate the invasion and colonization of distant organs. These findings suggest the use of antiplatelet agents to restrain cancer development and progression. Another peculiarity of platelets is their capability to uptake proteins and transcripts from the circulation. Thus, cancer-patient platelets show specific proteomic and transcriptomic expression patterns, a phenomenon called tumor-educated platelets (TEP). The transcriptomic/proteomic profile of platelets can provide information for the early detection of cancer and disease monitoring. Platelet ability to interact with tumor cells and transfer their molecular cargo has been exploited to design platelet-mediated drug delivery systems to enhance the efficacy and reduce toxicity often associated with traditional chemotherapy. Platelets are extraordinary cells with many functions whose exploitation will improve cancer diagnosis and treatment.

scholarly journals Electron Microscopic Immunogold Localization of Salivary Mucins MG1 and MG2 in Human Submandibular and Sublingual Glands

2003 ◽  
Vol 51 (1) ◽  
pp. 69-79 ◽  
Author(s):  
Marco Piludu ◽  
Sean A. Rayment ◽  
Bing Liu ◽  
Gwynneth D. Offner ◽  
Frank G. Oppenheim ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Expression Patterns ◽  
Cell Types ◽  
Mucous Cells ◽  
Electron Microscopic ◽  
Thin Sections ◽  
Dense Cores ◽  
Duct Cells ◽  
Rabbit Igg ◽  
Lowicryl K4m

The human salivary mucins MG1 and MG2 are well characterized biochemically and functionally. However, there is disagreement regarding their cellular and glandular sources. The aim of this study was to define the localization and distribution of these two mucins in human salivary glands using a postembedding immunogold labeling method. Normal salivary glands obtained at surgery were fixed in 3% paraformaldehyde-0.1% glutaraldehyde and embedded in Lowicryl K4M or LR Gold resin. Thin sections were labeled with rabbit antibodies to MG1 or to an N-terminal synthetic peptide of MG2, followed by gold-labeled goat anti-rabbit IgG. The granules of all mucous cells of the submandibular and sublingual glands were intensely reactive with anti-MG1. No reaction was detected in serous cells. With anti-MG2, the granules of both mucous and serous cells showed reactivity. The labeling was variable in both cell types, with mucous cells exhibiting a stronger reaction in some glands and serous cells in others. In serous granules, the electron-lucent regions were more reactive than the dense cores. Intercalated duct cells near the acini displayed both MG1 and MG2 reactivity in their apical granules. In addition, the basal and lateral membranes of intercalated duct cells were labeled with anti-MG2. These results confirm those of earlier studies on MG1 localization in mucous cells and suggest that MG2 is produced by both mucous and serous cells. They also indicate differences in protein expression patterns among salivary serous cells.

scholarly journals GABA receptors differentially regulate life span and health span in C. elegans through distinct downstream mechanisms

2019 ◽  
Vol 317 (5) ◽  
pp. C953-C963 ◽  
Author(s):  
Fengling Yuan ◽  
Jiejun Zhou ◽  
Lingxiu Xu ◽  
Wenxin Jia ◽  
Lei Chun ◽  
...  
Keyword(s):  
Life Span ◽  
Gaba Receptors ◽  
Health Span ◽  
Gaba A ◽  
Inhibitory Neurotransmitter ◽  
C Elegans ◽  
Physiological Processes ◽  
Gaba Signaling ◽  
Neuronal Functions

GABA, a prominent inhibitory neurotransmitter, is best known to regulate neuronal functions in the nervous system. However, much less is known about the role of GABA signaling in other physiological processes. Interestingly, recent work showed that GABA signaling can regulate life span via a metabotropic GABAB receptor in Caenorhabditis elegans. However, the role of other types of GABA receptors in life span has not been clearly defined. It is also unclear whether GABA signaling regulates health span. Here, using C. elegans as a model, we systematically interrogated the role of various GABA receptors in both life span and health span. We find that mutations in four different GABA receptors extend health span by promoting resistance to stress and pathogen infection and that two such receptor mutants also show extended life span. Different GABA receptors engage distinct transcriptional factors to regulate life span and health span, and even the same receptor regulates life span and health span via different transcription factors. Our results uncover a novel, profound role of GABA signaling in aging in C. elegans, which is mediated by different GABA receptors coupled to distinct downstream effectors.

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