Acid-Sensing Ion Channels

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.

scholarly journals Acid-sensing ion channels in sensory signaling

2020 ◽  
Vol 318 (3) ◽  
pp. F531-F543 ◽  
Author(s):  
Marcelo D. Carattino ◽  
Nicolas Montalbetti
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Genetically Modified ◽  
Physiological Processes ◽  
Acid Sensing Ion Channels ◽  
Genetically Modified Mice ◽  
Sensory Processes

Acid-sensing ion channels (ASICs) are cation-permeable channels that in the periphery are primarily expressed in sensory neurons that innervate tissues and organs. Soon after the cloning of the ASIC subunits, almost 20 yr ago, investigators began to use genetically modified mice to assess the role of these channels in physiological processes. These studies provide critical insights about the participation of ASICs in sensory processes, including mechanotransduction, chemoreception, and nociception. Here, we provide an extensive assessment of these findings and discuss the current gaps in knowledge with regard to the functions of ASICs in the peripheral nervous system.

Acid-Sensing Ion Channels: Focus on Physiological and Some Pathological Roles in the Brain

2021 ◽  
Vol 19 ◽  
Author(s):  
Maksim Storozhuka ◽  
Andrii Cherninskyia ◽  
Oleksandr Maximyuka ◽  
Dmytro Isaeva ◽  
Oleg Krishtala
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Mammalian Brain ◽  
Glutamatergic Synapses ◽  
Cellular Processes ◽  
Acid Sensing Ion Channels ◽  
Gabaergic Synapses ◽  
Function Relationship ◽  
The Brain

: Acid-sensing ion channels (ASICs) are Na+-permeable ion channels activated by protons and predominantly expressed in the nervous system. ASICs act as pH sensors leading to neuronal excitation. At least eight different ASIC subunits (including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4, ASIC5) are encoded by five genes (ASIC1–ASIC5). Functional ASICs assembled in the plasma membrane are homo- or heteromeric trimers. ASIC1a-containing trimers are of particular interest as, in addition to sodium ions, they also conduct calcium ions and thus can trigger or regulate multiple cellular processes. ASICs are widely, but differentially expressed in the central and peripheral nervous systems. In the mammalian brain a majority of neurons express at least one ASIC subunit. Several recent reviews have summarized findings about the role of ASICs in the peripheral nervous system, particularly in nociception and proprioception, and the structure-function relationship of ASICs. However, there is little coverage on recent findings regarding the role of ASICs in the brain. Here we review and discuss evidence regarding the roles of ASICs: (i) as postsynaptic receptors activated by protons co-released with glutamate at glutamatergic synapses; (ii) as modulators of synaptic transmission at glutamatergic synapses and GABAergic synapses; (iii) in synaptic plasticity, memory and learning; (iv) in some pathologies such as epilepsy, mood disorders and Alzheimer's disease.

Characterization of a Specific, High Affinity [3H]Arginine8Vasopressin-Binding Site on Liver Microsomes from Different Strains of Rat and the Role of Magnesium*

Endocrinology ◽  
1986 ◽  
Vol 118 (3) ◽  
pp. 990-998 ◽  
Author(s):  
VENKAT GOPALAKRISHNAN ◽  
CHRIS R. TRIGGLE ◽  
PRAKASH V. SULAKHE ◽  
J. ROBERT McNEILL
Keyword(s):  
Binding Site ◽  
Liver Microsomes ◽  
High Affinity ◽  
Different Strains

scholarly journals USG and CT scan evaluation of patients of acute and chronic pancreatitis- a cross-sectional, comparative study

2017 ◽  
Vol 5 (8) ◽  
pp. 3713 ◽  
Author(s):  
Aastha Bhatt ◽  
Awdhut Tiparse ◽  
Arpita Patel ◽  
Birwa Gandhi
Keyword(s):  
Ct Scan ◽  
Structural Changes ◽  
Radiation Hazard ◽  
Government Medical College ◽  
Detailed Characterization ◽  
Cross Sectional ◽  
Medical College ◽  
Adjacent Structures

Background: Pancreatitis is a condition of inflammation of pancreas with high rate of morbidity and mortality. USG provides the initial radiological assessment of the organ, clue of the extent of involvement and an opportunity to evaluate other abdominal organs. CT scan provides a cross-sectional anatomy of the organ, its internal structure, focal or diffuse involvement and involvement of adjacent structures. This study is done to evaluate the role of USG and CT scan in patients of pancreatitis admitted to Sir Takhtsinhji hospital, government medical college, Bhavnagar, Gujarat, India. Aim was to understand the role of CT and USG in determination of diagnosis of pancreatitis and to highlight and evaluate the cases in which USG failed to diagnose the cases which were helped through by CT.Methods: This study was done in department of radio diagnosis at Sir Takhtsinhji hospital, government medical college, Bhavnagar, Gujarat, India, over a period of one year from June 2015 to June 2016. Each patient was studied taking into consideration relevant clinical and laboratory factors. USG of patients was done using My Lab 40 or My Lab 20 plus machine. CT scan was done using GE 16 Slice CT scan machine.Results: Ultrasound by non-invasiveness, lack of radiation hazard and by ability to demonstrate structural changes in organ is first investigation of choice in pancreatitis. However, USG fails imaging in conditions with excess of bowel gas or fatty patient. It lacks in detailed characterization of the inflammatory process and does not delineate extent of necrosis of the gland. CT is superior to ultrasound for precise detection of size, parenchyma, MPD, calcification, pseudocyst, ascites, pleural effusion, necrosis and peri pancreatic region and hence helps to determine exact extent of inflammation of the organ, multi-system involvement and prognosis.Conclusions: Ultrasound by non-invasiveness, easy availability, cost parameters, lack of radiation hazard and by ability to demonstrate structural changes in organ is first investigation of choice in pancreatitis. However, ultrasonography lacks in detailed characterization of the extent of involvement of the organ and adjacent structures. CT is superior to ultrasound for precise detection and extension of the pancreatitis and it has better sensitivity and specificity than ultrasonography. 

scholarly journals Activation and activity of glycosylated KLKs 3, 4 and 11

2018 ◽  
Vol 399 (9) ◽  
pp. 1009-1022 ◽  
Author(s):  
Shihui Guo ◽  
Peter Briza ◽  
Viktor Magdolen ◽  
Hans Brandstetter ◽  
Peter Goettig
Keyword(s):  
Physiological Function ◽  
Periodic Acid ◽  
Hek293 Cells ◽  
Secretory Expression ◽  
Detailed Characterization ◽  
Periodic Acid Schiff ◽  
Clinical Biomarkers ◽  
Schiff Reaction

Abstract Human kallikrein-related peptidases 3, 4, 11, and KLK2, the activator of KLK3/PSA, belong to the prostatic group of the KLKs, whose major physiological function is semen liquefaction during the fertilization process. Notably, these KLKs are upregulated in prostate cancer and are used as clinical biomarkers or have been proposed as therapeutic targets. However, this potential awaits a detailed characterization of these proteases. In order to study glycosylated prostatic KLKs resembling the natural proteases, we used Leishmania (LEXSY) and HEK293 cells for secretory expression. Both systems allowed the subsequent purification of soluble pro-KLK zymogens with correct propeptides and of the mature forms. Periodic acid-Schiff reaction, enzymatic deglycosylation assays, and mass spectrometry confirmed the glycosylation of these KLKs. Activation of glycosylated pro-KLKs 4 and 11 turned out to be most efficient by glycosylated KLK2 and KLK4, respectively. By comparing the glycosylated prostatic KLKs with their non-glycosylated counterparts from Escherichia coli, it was observed that the N-glycans stabilize the KLK proteases and change their activation profiles and their enzymatic activity to some extent. The functional role of glycosylation in prostate-specific KLKs could pave the way to a deeper understanding of their biology and to medical applications.

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

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 401 ◽  
Author(s):  
Dmitry I. Osmakov ◽  
Sergey G. Koshelev ◽  
Igor A. Ivanov ◽  
Yaroslav A. Andreev ◽  
Sergey A. Kozlov
Keyword(s):  
Ion Channels ◽  
Dose Dependence ◽  
New Drugs ◽  
Induced Current ◽  
Acid Sensing Ion Channels ◽  
The Family ◽  
Dose Dependent Decrease ◽  
Dose Dependent ◽  
Gated Ion Channels

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.

scholarly journals Neural Control of Immunity in Hypertension: Council on Hypertension Mid Career Award for Research Excellence, 2019

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 622-628
Author(s):  
Daniela Carnevale
Keyword(s):  
Immune Response ◽  
Nervous System ◽  
Neural Control ◽  
Neural Signals ◽  
The Past ◽  
Target Organs ◽  
Long Time ◽  
The Common ◽  
The Brain

The nervous system and the immune system share the common ability to exert gatekeeper roles at the interfaces between internal and external environment. Although interaction between these 2 evolutionarily highly conserved systems has been recognized for long time, the investigation into the pathophysiological mechanisms underlying their crosstalk has been tackled only in recent decades. Recent work of the past years elucidated how the autonomic nervous system controls the splenic immunity recruited by hypertensive challenges. This review will focus on the neural mechanisms regulating the immune response and the role of this neuroimmune crosstalk in hypertension. In this context, the review highlights the components of the brain-spleen axis with a focus on the neuroimmune interface established in the spleen, where neural signals shape the immune response recruited to target organs of high blood pressure.

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