scholarly journals Acid-Sensing Ion Channels and Mechanosensation

2021 ◽  
Vol 22 (9) ◽  
pp. 4810
Author(s):  
Nina Ruan ◽  
Jacob Tribble ◽  
Andrew M. Peterson ◽  
Qian Jiang ◽  
John Q. Wang ◽  
...  
Keyword(s):  
Ion Channels ◽  
Underlying Mechanism ◽  
Cation Channels ◽  
Ischemic Brain Injury ◽  
Mechanical Forces ◽  
Sodium Permeability ◽  
Ischemic Brain ◽  
Acid Sensing Ion Channels ◽  
The Central Nervous System ◽  
Spring Mechanism

Acid-sensing ion channels (ASICs) are mainly proton-gated cation channels that are activated by pH drops and nonproton ligands. They are part of the degenerin/epithelial sodium channel superfamily due to their sodium permeability. Predominantly expressed in the central nervous system, ASICs are involved in synaptic plasticity, learning/memory, and fear conditioning. These channels have also been implicated in multiple disease conditions, including ischemic brain injury, multiple sclerosis, Alzheimer’s disease, and drug addiction. Recent research has illustrated the involvement of ASICs in mechanosensation. Mechanosensation is a form of signal transduction in which mechanical forces are converted into neuronal signals. Specific mechanosensitive functions have been elucidated in functional ASIC1a, ASIC1b, ASIC2a, and ASIC3. The implications of mechanosensation in ASICs indicate their subsequent involvement in functions such as maintaining blood pressure, modulating the gastrointestinal function, and bladder micturition, and contributing to nociception. The underlying mechanism of ASIC mechanosensation is the tether-gate model, which uses a gating-spring mechanism to activate ASIC responses. Further understanding of the mechanism of ASICs will help in treatments for ASIC-related pathologies. Along with the well-known chemosensitive functions of ASICs, emerging evidence has revealed that mechanosensitive functions of ASICs are important for maintaining homeostasis and contribute to various disease conditions.

scholarly journals Ion Channels and Zinc: Mechanisms of Neurotoxicity and Neurodegeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Deborah R. Morris ◽  
Cathy W. Levenson
Keyword(s):  
Brain Injury ◽  
Ion Channels ◽  
Kainate Receptors ◽  
Zinc Toxicity ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
The Central Nervous System ◽  
Excitatory Neurotransmission ◽  
The Brain

Ionotropic glutamate receptors, such as NMDA, AMPA and kainate receptors, are ligand-gated ion channels that mediate much of the excitatory neurotransmission in the brain. Not only do these receptors bind glutamate, but they are also regulated by and facilitate the postsynaptic uptake of the trace metal zinc. This paper discusses the role of the excitotoxic influx and accumulation of zinc, the mechanisms responsible for its cytotoxicity, and a number of disorders of the central nervous system that have been linked to these neuronal ion channels and zinc toxicity including ischemic brain injury, traumatic brain injury, and epilepsy.

scholarly journals Acid-sensing ion channels in mouse olfactory bulb M/T neurons

2014 ◽  
Vol 143 (6) ◽  
pp. 719-731 ◽  
Author(s):  
Ming-Hua Li ◽  
Selina Qiuying Liu ◽  
Koichi Inoue ◽  
Jinquan Lan ◽  
Roger P. Simon ◽  
...  
Keyword(s):  
Ion Channels ◽  
Olfactory Bulb ◽  
Calcium Concentration ◽  
Sensory System ◽  
Cation Channels ◽  
Olfactory Pathway ◽  
Whole Cell Patch Clamp ◽  
Acid Sensing Ion Channels ◽  
The Central Nervous System ◽  
Chemical Stimuli

The olfactory bulb contains the first synaptic relay in the olfactory pathway, the sensory system in which odorants are detected enabling these chemical stimuli to be transformed into electrical signals and, ultimately, the perception of odor. Acid-sensing ion channels (ASICs), a family of proton-gated cation channels, are widely expressed in neurons of the central nervous system. However, no direct electrophysiological and pharmacological characterizations of ASICs in olfactory bulb neurons have been described. Using a combination of whole-cell patch-clamp recordings and biochemical and molecular biological analyses, we demonstrated that functional ASICs exist in mouse olfactory bulb mitral/tufted (M/T) neurons and mainly consist of homomeric ASIC1a and heteromeric ASIC1a/2a channels. ASIC activation depolarized cultured M/T neurons and increased their intracellular calcium concentration. Thus, ASIC activation may play an important role in normal olfactory function.

Calcium-permeable Ion Channels and Ischemic Brain Injury

2012 ◽  
pp. 9-17
Author(s):  
Bentham Science Publisher Bentham Science Publisher
Keyword(s):  
Brain Injury ◽  
Ion Channels ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

scholarly journals Acid-sensing ion channels emerged over 600 Mya and are conserved throughout the deuterostomes

2018 ◽  
Vol 115 (33) ◽  
pp. 8430-8435 ◽  
Author(s):  
Timothy Lynagh ◽  
Yana Mikhaleva ◽  
Janne M. Colding ◽  
Joel C. Glover ◽  
Stephan A. Pless
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Sodium Current ◽  
Oikopleura Dioica ◽  
Acid Sensing Ion Channels ◽  
Mammalian Lineage ◽  
Molecular Determinants ◽  
Animal Phyla ◽  
The Central Nervous System ◽  
Functionally Diverse

Acid-sensing ion channels (ASICs) are proton-gated ion channels broadly expressed in the vertebrate nervous system, converting decreased extracellular pH into excitatory sodium current. ASICs were previously thought to be a vertebrate-specific branch of the DEG/ENaC family, a broadly conserved but functionally diverse family of channels. Here, we provide phylogenetic and experimental evidence that ASICs are conserved throughout deuterostome animals, showing that ASICs evolved over 600 million years ago. We also provide evidence of ASIC expression in the central nervous system of the tunicate, Oikopleura dioica. Furthermore, by comparing broadly related ASICs, we identify key molecular determinants of proton sensitivity and establish that proton sensitivity of the ASIC4 isoform was lost in the mammalian lineage. Taken together, these results suggest that contributions of ASICs to neuronal function may also be conserved broadly in numerous animal phyla.

scholarly journals Oligodendrocytes and Ischemic Brain Injury

2003 ◽  
Vol 23 (3) ◽  
pp. 263-274 ◽  
Author(s):  
Deborah Dewar ◽  
Suzanne M. Underhill ◽  
Mark P. Goldberg
Keyword(s):  
Demyelinating Disease ◽  
Acute Ischemia ◽  
Ischemic Brain Injury ◽  
Neurologic Diseases ◽  
Ischemic Brain ◽  
Highly Sensitive ◽  
Trophic Factor Deprivation ◽  
The Central Nervous System ◽  
Apoptotic Pathways ◽  
Myelin Injury

Oligodendrocytes, myelin-forming glial cells of the central nervous system, are vulnerable to damage in a variety of neurologic diseases. Much is known of primary myelin injury, which occurs in settings of genetic dysmyelination or demyelinating disease. There is growing awareness that oligodendrocytes are also targets of injury in acute ischemia. Recognition of oligodendrocyte damage in animal models of ischemia requires attention to their distinct histologic features or use of specific immunocytochemical markers. Like neurons, oligodendrocytes are highly sensitive to injury by oxidative stress, excitatory amino acids, trophic factor deprivation, and activation of apoptotic pathways. Understanding mechanisms of oligodendrocyte death may suggest new therapeutic strategies to preserve or restore white matter function and structure after ischemic insults.

scholarly journals Blockade of Acid-Sensing Ion Channels Increases Urinary Bladder Capacity With or Without Intravesical Irritation in Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Mitsuharu Yoshiyama ◽  
Hideki Kobayashi ◽  
Masayuki Takeda ◽  
Isao Araki
Keyword(s):  
Acetic Acid ◽  
Ion Channels ◽  
Urinary Bladder ◽  
Bladder Capacity ◽  
Saline Infusion ◽  
Acid Sensing Ion Channels ◽  
Vehicle Injection ◽  
The Central Nervous System ◽  
Bladder Activity

We conducted this study to examine whether acid-sensing ion channels (ASICs) are involved in the modulation of urinary bladder activity with or without intravesical irritation induced by acetic acid. All in vivo evaluations were conducted during continuous infusion cystometry in decerebrated unanesthetized female mice. During cystometry with a pH 6.3 saline infusion, an i.p. injection of 30 μmol/kg A-317567 (a potent, non-amiloride ASIC blocker) increased the intercontraction interval (ICI) by 30% (P < 0.001), whereas vehicle injection had no effect. An intravesical acetic acid (pH 3.0) infusion induced bladder hyperactivity, with reductions in ICI and maximal voiding pressure (MVP) by 79% (P < 0.0001) and 29% (P < 0.001), respectively. A-317567 (30 μmol/kg i.p.) alleviated hyperreflexia by increasing the acid-shortened ICI by 76% (P < 0.001). This dose produced no effect on MVP under either intravesical pH condition. Further analysis in comparison with vehicle showed that the increase in ICI (or bladder capacity) by the drug was not dependent on bladder compliance. Meanwhile, intravesical perfusion of A-317567 (100 μM) had no effect on bladder activity during pH 6.0 saline infusion cystometry, and drug perfusion at neither 100 μM nor 1 mM produced any effects on bladder hyperreflexia during pH 3.0 acetic acid infusion cystometry. A-317567 has been suggested to display extremely poor penetrability into the central nervous system and thus to be a peripherally active blocker. Taken together, our results suggest that blockade of ASIC signal transduction increases bladder capacity under normal intravesical pH conditions and alleviates bladder hyperreflexia induced by intravesical acidification and that the site responsible for this action is likely to be the dorsal root ganglia.

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