Acid-Sensing Ion Channels Contribute to Neurotoxicity

Chu, Xiang‐Ping; Grasing, Kenneth; Wang, John Q.

doi:10.1007/s12975-013-0305-y

Cited by 25 publications

(34 citation statements)

References 105 publications

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“…Moreover, PcTx1 decreases the acidosis-mediated cell death in cultured retinal ganglion cells [74]. Collectively, all the results support that PcTx1 might be a potential therapeutic agent for neurological disease [9,12,81,87,88].…”

Section: Targeting Asics By Peptide Toxins 21 Psalmotoxin-1 (Pctx1)mentioning

confidence: 71%

“…ASIC currents and/ or transcripts have also been found in glia, smooth muscle cells, lung epithelial cells, immune cells, urothelial cells, adipose cells, joint cells and osteoclasts, indicating that ASICs likely play a role in non-neuronal cells as well [18,32,35,50,59,70,86]. The review regarding the effects of peptide toxins on ASICs has also been discussed by previous publications [4,5,9,10,12,17].…”

Section: Introductionmentioning

confidence: 95%

“…At concentrations that effectively inhibit the homomeric ASIC1a current, it has no effect on the currents mediated by other configurations of ASICs such as heteromeric ASIC1a/2a channels [31] or known voltage-gated Na + , K + , Ca 2+ channels as well as several ligandgated ion channels [89]. Unlike amiloride, which is a blocker of epithelial sodium channel and directly blocks the ASICs, PcTx1 acts as a gating modifier [9,35]. PcTx1 shifts the channel from its resting state toward the inactivated state by increasing its apparent affinity for protons [5,17].…”

Section: Targeting Asics By Peptide Toxins 21 Psalmotoxin-1 (Pctx1)mentioning

confidence: 99%

“…ASICs are mainly expressed in the central and peripheral nervous systems, chiefly found in neurons [80,82]. In central nervous system, ASICs contributed to several physiological and pathological conditions, such as learning and memory, fear conditioning, pain, chemoreception, ischemia, seizures, drug addiction and neuroinflammation, where extracellular acidification occurs [5,9,12,[82][83][84]. More importantly, ASICs are involved in synaptic physiology and are neurotransmitter receptors critical for amygdala-dependent learning and memory [26].…”

Section: Introductionmentioning

confidence: 99%

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Targeting Acid-Sensing Ion Channels by Peptide Toxins

Li¹,

Wang²,

Chu³

2018

Neurotoxins

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Acid-sensing ion channels (ASICs) are proton-gated ion channels that are highly expressed in the nervous system and play important roles in physiological and pathological conditions. They are also expressed in non-neuronal tissues with different functions. The ASICs rapidly respond to a reduction in extracellular pH with an inward current that is quickly inactivated despite the continuous presence of protons. Recently, protons have been identified as neurotransmitters in the brain. Until now, six different isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) in rodents have been discovered and they can be assembled into homotrimers or heterotrimers to form an ion channel. Peptide toxins targeting ASICs have been found from the venoms of spider Psalmotoxin-1 (PcTx1), sea anemones (APETx2 and PhcrTx1) and snakes (MitTx and mambalgins). They reveal different pharmacological properties and are selective blockers of ASICs, except for MitTx, which is a potent activator of ASICs. In this mini review, the structure, pharmacology and effects of peptide toxins on ASICs will be introduced and their therapeutic potentials for neurological and psychological diseases will be discussed.

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Section: Targeting Asics By Peptide Toxins 21 Psalmotoxin-1 (Pctx1)mentioning

confidence: 71%

Section: Introductionmentioning

confidence: 95%

Section: Targeting Asics By Peptide Toxins 21 Psalmotoxin-1 (Pctx1)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeting Acid-Sensing Ion Channels by Peptide Toxins

Li¹,

Wang²,

Chu³

2018

Neurotoxins

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“…ASIC2b and ASIC4 cannot form functional homomeric channels101213, but they can associate with other ASIC subunit(s) to form functional heteromeric ASICs151617. Among all ASIC subunits, ASIC1a and ASIC2 are the two most abundant subunits within the central nervous system (CNS) and play important roles in physiological and pathophysiological conditions1819. ASIC1a is widely expressed in the CNS including the cortex, striatum, hippocampus, amygdala and hypothalamus32021.…”

mentioning

confidence: 99%

Acid-sensing ion channels are expressed in the ventrolateral medulla and contribute to central chemoreception

Song

Guan

Jiang

et al. 2016

Sci Rep

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The role of acid-sensing ion channels (ASICs) in the ventrolateral medulla (VLM) remains uncertain. Here, we found that ASIC1a and ASIC2 are widely expressed in rat medulla, and the expression level is higher at neonatal stage as compared to adult stage. The two ASIC subunits co-localized in medualla neurons. Furthermore, pH reduction triggered typical ASIC-type currents in the medulla, including the VLM. These currents showed a pH50 value of 6.6 and were blocked by amiloride. Based on their sensitivity to psalmotoxin 1 (PcTx1) and zinc, homomeric ASIC1a and heteromeric ASIC1a/2 channels were likely responsible for acid-mediated currents in the mouse medulla. ASIC currents triggered by pH 5 disappeared in the VLM neurons from ASIC1−/−, but not ASIC2−/− mice. Activation of ASICs in the medulla also triggered neuronal excitation. Moreover, microinjection of artificial cerebrospinal fluid at a pH of 6.5 into the VLM increased integrated phrenic nerve discharge, inspiratory time and respiratory drive in rats. Both amiloride and PcTx1 inhibited the acid-induced stimulating effect on respiration. Collectively, our data suggest that ASICs are highly expressed in the medulla including the VLM, and activation of ASICs in the VLM contributes to central chemoreception.

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Drugs/agents for the treatment of ischemic stroke: Advances and perspectives

Jia,

Jiao,

Wang

et al. 2023

Medicinal Research Reviews

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Ischemic stroke (IS) poses a significant threat to global human health and life. In recent decades, we have witnessed unprecedented progresses against IS, including thrombolysis, thrombectomy, and a few medicines that can assist in reopening the blocked brain vessels or serve as standalone treatments for patients who are not eligible for thrombolysis/thrombectomy therapies. However, the narrow time windows of thrombolysis/thrombectomy, coupled with the risk of hemorrhagic transformation, as well as the lack of highly effective and safe medications, continue to present big challenges in the acute treatment and long‐term recovery of IS. In the past 3 years, several excellent articles have reviewed pathophysiology of IS and therapeutic medicines for the treatment of IS based on the pathophysiology. Regretfully, there is no comprehensive overview to summarize all categories of anti‐IS drugs/agents designed and synthesized based on molecular mechanisms of IS pathophysiology. From medicinal chemistry view of point, this article reviews a multitude of anti‐IS drugs/agents, including small molecule compounds, natural products, peptides, and others, which have been developed based on the molecular mechanism of IS pathophysiology, such as excitotoxicity, oxidative/nitrosative stresses, cell death pathways, and neuroinflammation, and so forth. In addition, several emerging medicines and strategies, including nanomedicines, stem cell therapy and noncoding RNAs, which recently appeared for the treatment of IS, are shortly introduced. Finally, the perspectives on the associated challenges and future directions of anti‐IS drugs/agents are briefly provided to move the field forward.

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Acid-Sensing Ion Channels Contribute to Neurotoxicity

Cited by 25 publications

References 105 publications

Targeting Acid-Sensing Ion Channels by Peptide Toxins

Targeting Acid-Sensing Ion Channels by Peptide Toxins

Acid-sensing ion channels are expressed in the ventrolateral medulla and contribute to central chemoreception

Drugs/agents for the treatment of ischemic stroke: Advances and perspectives

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