scholarly journals Distinct roles for two Caenorhabditis elegans acid-sensing ion channels in an ultradian clock

2021 ◽  
Author(s):  
Eva Kaulich ◽  
Brian D Ackley ◽  
Yi Quan Tang ◽  
Iris Hardege ◽  
William Schafer ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Ion Channels ◽  
Ph Regulation ◽  
Basolateral Membrane ◽  
Motor Program ◽  
Biological Clocks ◽  
Sensing Properties ◽  
Metabolic Defects ◽  
Acid Sensing Ion Channels ◽  
Intracellular Ca

Biological clocks are fundamental to an organism′s health, controlling periodicity of behavior and metabolism. Here, we identify two acid-sensing ion channels, with very different proton sensing properties, and describe their role in an ultradian clock, the defecation motor program (DMP) of the nematode Caenorhabditis elegans. An ACD-5-containing channel, on the apical membrane of the intestinal epithelium, is essential for maintenance of luminal acidity, and thus the rhythmic oscillations in lumen pH. In contrast, the second channel, composed of FLR-1, ACD-3 and/or DEL-5, located on the basolateral membrane, controls the intracellular Ca2+ wave and forms a core component of the master oscillator that controls timing and rhythmicity of the DMP. flr-1 and acd-3/del-5 mutants show severe developmental and metabolic defects. We thus directly link the proton-sensing properties of these channels to their physiological roles in pH regulation and Ca2+ signaling, the generation of an ultradian oscillator, and its metabolic consequences.

scholarly journals Acid-Sensing Ion Channels in Acidosis-Induced Injury of Human Brain Neurons

2010 ◽  
Vol 30 (6) ◽  
pp. 1247-1260 ◽  
Author(s):  
Minghua Li ◽  
Koichi Inoue ◽  
Deborah Branigan ◽  
Eric Kratzer ◽  
Jillian C Hansen ◽  
...  
Keyword(s):  
Ion Channels ◽  
Human Brain ◽  
Cortical Neurons ◽  
Cell Injury ◽  
Acidic Solution ◽  
Brain Neurons ◽  
Acid Sensing Ion Channels ◽  
Intracellular Ca ◽  
Inward Currents ◽  
High Level

Acidosis is a common feature of the human brain during ischemic stroke and is known to cause neuronal injury. However, the mechanism underlying acidosis-mediated injury of the human brain remains elusive. We show that a decrease in the extracellular pH evoked inward currents characteristic of acid-sensing ion channels (ASICs) and increased intracellular Ca2+ in cultured human cortical neurons. Acid-sensing ion channels in human cortical neurons show electrophysiological and pharmacological properties distinct from those in neurons of the rodent brain. Reverse transcriptase-PCR and western blot detected a high level of the ASIC1a subunit with little or no expression of other ASIC subunits. Treatment of human cortical neurons with acidic solution induced substantial cell injury, which was attenuated by the ASIC1a blockade. Thus, functional homomeric ASIC1a channels are predominantly expressed in neurons from the human brain. Activation of these channels has an important role in acidosis-mediated injury of human brain neurons.

Acid-sensing ion channels

2006 ◽  
pp. S100-S101
Author(s):  
S P H Alexander ◽  
A Mathie ◽  
J A Peters
Keyword(s):  
Ion Channels ◽  
Acid Sensing Ion Channels

Acid Sensing Ion Channels (ASICs) und 5-HT-Rezeptoren bei GERD. Untersuchungen zur Genexpression im pharmakologischen Modell

2015 ◽  
Vol 53 (08) ◽  
Author(s):  
A Shcherbokova ◽  
H Abdel-Aziz ◽  
O Kelber ◽  
K Nieber ◽  
G Ulrich-Merzenich
Keyword(s):  
Ion Channels ◽  
Acid Sensing Ion Channels

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.

Innate immune response in CF airway epithelia: hyperinflammatory?

2006 ◽  
Vol 291 (2) ◽  
pp. C218-C230 ◽  
Author(s):  
Terry E. Machen
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Innate Immune Response ◽  
Cellular Signaling ◽  
Basolateral Membrane ◽  
Airway Epithelial Cells ◽  
Innate Immune ◽  
Airway Epithelial ◽  
Airway Epithelia ◽  
Intracellular Ca

The lack of functional cystic fibrosis (CF) transmembrane conductance regulator (CFTR) in the apical membranes of CF airway epithelial cells abolishes cAMP-stimulated anion transport, and bacteria, eventually including Pseudomonas aeruginosa, bind to and accumulate in the mucus. Flagellin released from P. aeruginosa triggers airway epithelial Toll-like receptor 5 and subsequent NF-κB signaling and production and release of proinflammatory cytokines that recruit neutrophils to the infected region. This response has been termed hyperinflammatory because so many neutrophils accumulate; a response that damages CF lung tissue. We first review the contradictory data both for and against the idea that epithelial cells exhibit larger-than-normal proinflammatory signaling in CF compared with non-CF cells and then review proposals that might explain how reduced CFTR function could activate such proinflammatory signaling. It is concluded that apparent exaggerated innate immune response of CF airway epithelial cells may have resulted not from direct effects of CFTR on cellular signaling or inflammatory mediator production but from indirect effects resulting from the absence of CFTRs apical membrane channel function. Thus, loss of Cl−, HCO3−, and glutathione secretion may lead to reduced volume and increased acidification and oxidation of the airway surface liquid. These changes concentrate proinflammatory mediators, reduce mucociliary clearance of bacteria and subsequently activate cellular signaling. Loss of apical CFTR will also hyperpolarize basolateral membrane potentials, potentially leading to increases in cytosolic [Ca2+], intracellular Ca2+, and NF-κB signaling. This hyperinflammatory effect of CF on intracellular Ca2+and NF-κB signaling would be most prominently expressed during exposure to both P. aeruginosa and also endocrine, paracrine, or nervous agonists that activate Ca2+signaling in the airway epithelia.

scholarly journals Acid sensing ion channels regulate neuronal excitability by inhibiting BK potassium channels

2012 ◽  
Vol 426 (4) ◽  
pp. 511-515 ◽  
Author(s):  
Elena Petroff ◽  
Vladislav Snitsarev ◽  
Huiyu Gong ◽  
Francois M. Abboud
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Neuronal Excitability ◽  
Acid Sensing Ion Channels

scholarly journals The function and regulation of acid-sensing ion channels (ASICs) and the epithelial Na+channel (ENaC): IUPHAR Review 19

2016 ◽  
Vol 173 (18) ◽  
pp. 2671-2701 ◽  
Author(s):  
Emilie Boscardin ◽  
Omar Alijevic ◽  
Edith Hummler ◽  
Simona Frateschi ◽  
Stephan Kellenberger
Keyword(s):  
Ion Channels ◽  
Na Channel ◽  
Acid Sensing Ion Channels ◽  
Epithelial Na Channel
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