Endogenous Neuropeptide Nocistatin Is a Direct Agonist of Acid-Sensing Ion Channels (ASIC1, ASIC2 and ASIC3)

Acid-sensing ion channel (ASIC) channels belong to the family of ligand-gated ion channels known as acid-sensing (proton-gated) ion channels. Only a few activators of ASICs are known. These are exogenous and endogenous molecules that cause a persistent, slowly desensitized current, different from an acid-induced current. Here we describe a novel endogenous agonist of ASICs—peptide nocistatin produced by neuronal cells and neutrophils as a part of prepronociceptin precursor protein. The rat nocistatin evoked currents in X. laevis oocytes expressing rat ASIC1a, ASIC1b, ASIC2a, and ASIC3 that were very similar in kinetic parameters to the proton-gated response. Detailed characterization of nocistatin action on rASIC1a revealed a proton-like dose-dependence of activation, which was accompanied by a dose-dependent decrease in the sensitivity of the channel to the protons. The toxin mambalgin-2, antagonist of ASIC1a, inhibited nocistatin-induced current, therefore the close similarity of mechanisms for ASIC1a activation by peptide and protons could be suggested. Thus, nocistatin is the first endogenous direct agonist of ASICs. This data could give a key to understanding ASICs activation regulation in the nervous system and also could be used to develop new drugs to treat pathological processes associated with ASICs activation, such as neurodegeneration, inflammation, and pain.

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Acid-Sensing Ion Channels

The Oxford Handbook of Neuronal Ion Channels ◽

10.1093/oxfordhb/9780190669164.013.12 ◽

2020 ◽

Author(s):

Stefan Gründer

Keyword(s):

Nervous System ◽

Ion Channels ◽

Excitatory Synapses ◽

Detailed Characterization ◽

High Affinity ◽

Acid Sensing Ion Channels ◽

Long Time ◽

Pathological Pain

Acid-sensing ion channels (ASICs) are proton-gated Na+ channels. Being almost ubiquitously present in neurons of the vertebrate nervous system, their precise function remained obscure for a long time. Various animal toxins that bind to ASICs with high affinity and specificity have been tremendously helpful in uncovering the role of ASICs. We now know that they contribute to synaptic transmission at excitatory synapses as well as to sensing metabolic acidosis and nociception. Moreover, detailed characterization of mouse models uncovered an unanticipated role of ASICs in disorders of the nervous system like stroke, multiple sclerosis, and pathological pain. This review provides an overview on the expression, structure, and pharmacology of ASICs plus a summary of what is known and what is still unknown about their physiological functions and their roles in diseases.

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Characterization of Excitability and Voltage-gated Ion Channels of Neural Progenitor Cells in Rat Hippocampus

Journal of Molecular Neuroscience ◽

10.1007/s12031-008-9065-7 ◽

2008 ◽

Vol 35 (3) ◽

pp. 289-295 ◽

Cited By ~ 15

Author(s):

Tingsong Li ◽

Li Jiang ◽

Hengsheng Chen ◽

Xiaoping Zhang

Keyword(s):

Ion Channels ◽

Progenitor Cells ◽

Neural Progenitor Cells ◽

Neural Progenitor ◽

Rat Hippocampus ◽

Voltage Gated ◽

Voltage Gated Ion Channels ◽

Gated Ion Channels

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Characterization of the interaction between a novel convulsant agent, norbiphen, and GABAA and other ligand-gated ion channels

Neuropharmacology ◽

10.1016/s0028-3908(02)00173-9 ◽

2002 ◽

Vol 43 (4) ◽

pp. 778-787 ◽

Cited By ~ 6

Author(s):

R.F. Halliwell ◽

Jiping Su ◽

A. Demuro ◽

A. Martinez-Torres ◽

R. Miledi

Keyword(s):

Ion Channels ◽

Gated Ion Channels ◽

Ligand Gated Ion Channels

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Acid-sensing ion channels are involved in epithelial Na+ uptake in the rainbow trout Oncorhynchus mykiss

AJP Cell Physiology ◽

10.1152/ajpcell.00398.2013 ◽

2014 ◽

Vol 307 (3) ◽

pp. C255-C265 ◽

Cited By ~ 33

Author(s):

Agnieszka K. Dymowska ◽

Aaron G. Schultz ◽

Salvatore D. Blair ◽

Danuta Chamot ◽

Greg G. Goss

Keyword(s):

Rainbow Trout ◽

Ion Channels ◽

Three Dimensional ◽

Immunohistochemical Analysis ◽

Apical Region ◽

Dependent Manner ◽

Rainbow Trout Oncorhynchus Mykiss ◽

Acid Sensing Ion Channels ◽

Custom Made ◽

Dose Dependent

A role for acid-sensing ion channels (ASICs) to serve as epithelial channels for Na+ uptake by the gill of freshwater rainbow trout was investigated. We found that the ASIC inhibitors 4′,6-diamidino-2-phenylindole and diminazene decreased Na+ uptake in adult rainbow trout in a dose-dependent manner, with IC50 values of 0.12 and 0.96 μM, respectively. Furthermore, we cloned the trout ASIC1 and ASIC4 homologs and demonstrated that they are expressed differentially in the tissues of the rainbow trout, including gills and isolated mitochondrion-rich cells. Immunohistochemical analysis using custom-made anti-zASIC4.2 antibody and the Na+-K+-ATPase (α5-subunit) antibody demonstrated that the trout ASIC localizes to Na+/K+-ATPase-rich cells in the gill. Moreover, three-dimensional rendering of confocal micrographs demonstrated that ASIC is found in the apical region of mitochondrion-rich cells. We present a revised model whereby ASIC4 is proposed as one mechanism for Na+ uptake from dilute freshwater in the gill of rainbow trout.

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Characterization of Gating Mechanisms in Prokaryotic Pentameric Ligand-Gated Ion Channels

Biophysical Journal ◽

10.1016/j.bpj.2011.11.641 ◽

2012 ◽

Vol 102 (3) ◽

pp. 114a

Author(s):

Phanindra Velisetty ◽

Sudha Chakrapani

Keyword(s):

Ion Channels ◽

Gating Mechanisms ◽

Gated Ion Channels ◽

Ligand Gated Ion Channels

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Current Pharmacologic Strategies for Treatment of Intractable Epilepsy in Children

International Neurourology Journal ◽

10.5213/inj.2142166.083 ◽

2021 ◽

Vol 25 (Suppl 1) ◽

pp. S8-18 ◽

Cited By ~ 1

Author(s):

Ja Un Moon ◽

Kyung-Ok Cho

Keyword(s):

Ion Channels ◽

Molecular Mechanisms ◽

Intractable Epilepsy ◽

Epileptic Encephalopathy ◽

New Drugs ◽

Dravet Syndrome ◽

Ohtahara Syndrome ◽

Voltage Gated Ion Channels ◽

Related Proteins ◽

Gated Ion Channels

Epileptic encephalopathy (EE) is a devastating pediatric disease that features medically resistant seizures, which can contribute to global developmental delays. Despite technological advancements in genetics, the neurobiological mechanisms of EEs are not fully understood, leaving few therapeutic options for affected patients. In this review, we introduce the most common EEs in pediatrics (i.e., Ohtahara syndrome, Dravet syndrome, and Lennox-Gastaut syndrome) and their molecular mechanisms that cause excitation/inhibition imbalances. We then discuss some of the essential molecules that are frequently dysregulated in EEs. Specifically, we explore voltage-gated ion channels, synaptic transmission-related proteins, and ligand-gated ion channels in association with the pathophysiology of Ohtahara syndrome, Dravet syndrome, and Lennox-Gastaut syndrome. Finally, we review currently available antiepileptic drugs used to treat seizures in patients with EEs. Since these patients often fail to achieve seizure relief even with the combination therapy, further extensive research efforts to explore the involved molecular mechanisms will be required to develop new drugs for patients with intractable epilepsy.

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Characterization of Chlamydia pneumoniae Persistence in HEp-2 Cells Treated with Gamma Interferon

Infection and Immunity ◽

10.1128/iai.69.12.7927-7932.2001 ◽

2001 ◽

Vol 69 (12) ◽

pp. 7927-7932 ◽

Cited By ~ 60

Author(s):

Laura G. Pantoja ◽

Richard D. Miller ◽

Julio A. Ramirez ◽

Robert E. Molestina ◽

James T. Summersgill

Keyword(s):

Risk Factor ◽

Chlamydia Pneumoniae ◽

Gamma Interferon ◽

Phenotypic Switch ◽

Inclusion Morphology ◽

Ifn Γ ◽

Dose Dependent Decrease ◽

Dose Dependent ◽

Dioxygenase Activity

ABSTRACT Infection with Chlamydia pneumoniae has been implicated as a potential risk factor for atherosclerosis. This study demonstrated the effects of gamma interferon (IFN-γ)-mediated indoleamine 2,3-dioxygenase activity on C. pneumoniaepersistence in HEp-2 cells, inclusion morphology, and ultrastructure.C. pneumoniae replication showed a dose-dependent decrease when treated with increasing concentrations of IFN-γ and a phenotypic switch resulting in a decrease in typical inclusions with an increase in smaller, less-dense atypical inclusions. Ultrastructural analysis of IFN-γ-treated C. pneumoniae revealed atypical inclusions containing large reticulatate-like aberrant bodies with no evidence of redifferentiation into elementary bodies.

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Effect of Adenosine and Adenosine Receptor Antagonists on Retinal Müller Cell Inwardly Rectifying Potassium Channels under Exogenous Glutamate Stimulation

BioMed Research International ◽

10.1155/2018/2749257 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10

Author(s):

Zhongjing Lin ◽

Ping Huang ◽

Shouyue Huang ◽

Lei Guo ◽

Xing Xu ◽

...

Keyword(s):

Müller Cells ◽

Muller Cells ◽

Digestion Method ◽

Expression Levels ◽

Inwardly Rectifying Potassium Channels ◽

Dose Dependent Decrease ◽

Inwardly Rectifying ◽

Dose Dependent ◽

Papain Digestion

The vitreousness of glaucoma subjects contains elevated glutamate, and excessive extracellular glutamate is toxic to retinal neurons. Therefore, glutamate clearance is potentially impaired in the retina of glaucoma subjects. Müller cells play an important role in maintaining low extracellular levels of neurotransmitters, such as glutamate. A better understanding of the cross-talk between adenosine and glutamate may provide a better characterization of the regulatory network in Müller cells. Here, Müller cells were purified from the rat retina on postnatal day 5 using the papain digestion method. Application of increasing concentrations of glutamate (0-20 mmol/L) caused a dose-dependent decrease in the expression levels of Kir4.1, Kir2.1, GLAST, and GS. Exogenous adenosine regulated Kir channels and subsequently promoted GLAST and GS expression levels in Müller cells under exogenous glutamate stimulation. These effects were partly dependent on adenosine receptors.

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