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.

scholarly journals Hydrogen sulfide upregulates acid-sensing ion channels via the MAPK-Erk1/2 signaling pathway

Function ◽  
2021 ◽  
Author(s):  
Zhong Peng ◽  
Stephan Kellenberger
Keyword(s):  
Hydrogen Sulfide ◽  
Ion Channels ◽  
Signaling Pathway ◽  
Cortical Neurons ◽  
Mammalian Cells ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Membrane Expression ◽  
Concentration Dependent Manner ◽  
Acid Sensing Ion Channels

Abstract Hydrogen sulfide (H2S) emerged recently as a new gasotransmitter and was shown to exert cellular effects by interacting with proteins, among them many ion channels. Acid-sensing ion channels (ASICs) are neuronal voltage-insensitive Na+ channels activated by extracellular protons. ASICs are involved in many physiological and pathological processes, such as fear conditioning, pain sensation and seizures. We characterize here the regulation of ASICs by H2S. In transfected mammalian cells, the H2S donor NaHS increased the acid-induced ASIC1a peak currents in a time- and concentration-dependent manner. Similarly, NaHS potentiated also the acid-induced currents of ASIC1b, ASIC2a and ASIC3. An upregulation induced by the H2S donors NaHS and GYY4137 was also observed with the endogenous ASIC currents of cultured hypothalamus neurons. In parallel with the effect on function, the total and plasma membrane expression of ASIC1a was increased by GYY4137, as determined in cultured cortical neurons. H2S also enhanced the phosphorylation of extracellular signal-regulated kinase, which belongs to the family of mitogen-activated protein kinases (MAPKs). Pharmacological blockade of the MAPK signaling pathway prevented the GYY4137-induced increase of ASIC function and expression, indicating that this pathway is required for ASIC regulation by H2S. Our study demonstrates that H2S regulates ASIC expression and function, and identifies the involved signaling mechanism. Since H2S shares several roles with ASICs, as e.g. facilitation of learning and memory, protection during seizure activity and modulation of nociception, it may be possible that H2S exerts some of these effects via a regulation of ASIC function.

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 Role of transporters and ion channels in neuronal injury under hypoxia

2008 ◽  
Vol 294 (2) ◽  
pp. R451-R457 ◽  
Author(s):  
Jin Xue ◽  
Dan Zhou ◽  
Hang Yao ◽  
Gabriel G. Haddad
Keyword(s):  
Ion Channels ◽  
Cortical Neurons ◽  
Cell Injury ◽  
Neuronal Damage ◽  
Hippocampal Slices ◽  
Neuronal Injury ◽  
Hypoxic Injury ◽  
Significant Difference ◽  
Cultured Cortical Neurons

The aims of the current study were to 1) examine the effects of hypoxia and acidosis on cultured cortical neurons and 2) explore the role of transporters and ion channels in hypoxic injury. Cell injury was measured in cultured neurons or hippocampal slices following hypoxia (1% O2) or acidosis (medium pH 6.8) treatment. Inhibitors of transporters and ion channels were employed to investigate their roles in hypoxic injury. Our results showed that 1) neuronal damage was apparent at 5–7 days of hypoxia exposure, i.e., 36–41% of total lactate dehydrogenase was released to medium and 2) acidosis alone did not lead to significant injury compared with nonacidic, normoxic controls. Pharmacological studies revealed 1) no significant difference in neuronal injury between controls (no inhibitor) and inhibition of Na+-K+-ATP pump, voltage-gated Na+ channel, ATP-sensitive K+ channel, or reverse mode of Na+/Ca2+ exchanger under hypoxia; however, 2) inhibition of NBCs with 500 μM DIDS did not cause hypoxic death in either cultured cortical neurons or hippocampal slices; 3) in contrast, inhibition of Na+/H+ exchanger isoform 1 (NHE1) with either 10 μM HOE-642 or 2 μM T-162559 resulted in dramatic hypoxic injury (+95% for HOE-642 and +100% for T-162559 relative to normoxic control, P < 0.001) on treatment day 3, when no death occurred for hypoxic controls (no inhibitor). No further damage was observed by NHE1 inhibition on treatment day 5. We conclude that inhibition of NHE1 accelerates hypoxia-induced neuronal damage. In contrast, DIDS rescues neuronal death under hypoxia. Hence, DIDS-sensitive mechanism may be a potential therapeutic target.

scholarly journals Mechanically Induced Integrin Ligation Mediates Intracellular Calcium Signaling with Single Pulsating Cavitation Bubbles

2020 ◽  
Author(s):  
Fenfang Li ◽  
Tae Hyun Park ◽  
George Sankin ◽  
Christopher Gilchrist ◽  
Defei Liao ◽  
...  
Keyword(s):  
Ion Channels ◽  
Cell Injury ◽  
Atp Release ◽  
Apical Surface ◽  
Cavitation Bubbles ◽  
Intracellular Calcium Signaling ◽  
Intracellular Ca ◽  
Spread Area ◽  
Membrane Poration ◽  
Blocking Antibodies

Ultrasound or shockwave-induced cavitation is used therapeutically to stimulate neural and muscle tissue, but the mechanisms underlying this mechanotransduction are unclear. Intracellular Ca2+ signaling is one of the earliest events in mechanotransduction. In this study, we investigate the mechanism of Ca2+ signaling in individual HEK293T cells stimulated by single cavitation bubbles. Ca2+ responses are rare at cell-bubble distance that avoids membrane poration, even with overexpression of the mechanosensitive ion channel Piezo1, but could be increased in frequency to 42% of cells by attaching RGD beads to the apical surface of the cells. By using Piezo1 knockout and Piezo1-expressing cells, integrin-blocking antibodies, and inhibitors of P2X ion channels, key molecular players are identified in the RGD bead-enhanced Ca2+ response: increased integrin ligation by substrate ECM triggers ATP release and activation of P2X—but not Piezo1—ion channels. These molecular players have not been examined previously in cavitation-induced Ca2+ signaling. The resultant Ca2+ influx causes dynamic changes in cell spread area. This approach to eliciting a Ca2+ response with cavitation microbubbles without cell injury, and the uncovered mechanotransduction mechanism by which increased integrin-ligation mediates ATP release and Ca2+ signaling will inform new strategies to stimulate tissues with ultrasound and shockwaves.

Acid-sensing ion channels contribute to the increase in vesicular release from SH-SY5Y cells stimulated by extracellular protons

2012 ◽  
Vol 303 (4) ◽  
pp. C376-C384 ◽  
Author(s):  
Qiu-Ju Xiong ◽  
Zhuang-Li Hu ◽  
Peng-Fei Wu ◽  
Lan Ni ◽  
Zhi-Fang Deng ◽  
...  
Keyword(s):  
Ion Channels ◽  
Neurotransmitter Release ◽  
Neuronal Cell ◽  
Channel Blockers ◽  
Patch Clamp Recording ◽  
Human Neuroblastoma ◽  
Whole Cell Patch Clamp ◽  
Acid Sensing Ion Channels ◽  
Vesicular Release ◽  
Inward Currents

Acid-sensing ion channels (ASICs) have been reported to play a role in the neuronal dopamine pathway, but the exact role in neurotransmitter release remains elusive. Human neuroblastoma SH-SY5Y is a dopaminergic neuronal cell line, which can release monoamine neurotransmitters. In this study, the expression of ASICs was identified in SH-SY5Y cells to further explore the role of ASICs in vesicular release stimulated by acid. We gathered evidence that ASICs could be detected in SH-SY5Y cells. In whole cell patch-clamp recording, a rapid decrease in extracellular pH evoked inward currents, which were reversibly inhibited by 100 μM amiloride. The currents were pH dependent, with a pH of half-maximal activation (pH0.5) of 6.01 ± 0.04. Furthermore, in calcium imaging and FM 1-43 dye labeling, it was shown that extracellular protons increased intracellular calcium levels and vesicular release in SH-SY5Y cells, which was attenuated by PcTx1 and amiloride. Interestingly, N-type calcium channel blockers inhibited the vesicular release induced by acidification. In conclusion, ASICs are functionally expressed in SH-SY5Y cells and involved in vesicular release stimulated by acidification. N-type calcium channels may be involved in the increase in vesicular release induced by acid. Our results provide a preliminary study on ASICs in SH-SY5Y cells and neurotransmitter release, which helps to further investigate the relationship between ASICs and dopaminergic 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.

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