Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a

Yermolaieva, Olena; Leonard, A. Soren; Schnizler, M.; Abboud, François M.; Welsh, Michael J.

doi:10.1073/pnas.0308636100

Cited by 345 publications

(402 citation statements)

References 45 publications

Supporting

Mentioning

386

Contrasting

Unclassified

Order By: Relevance

“…This acid-induced increase of [Ca 2+ ] i could be recorded in the presence of a cocktail blocking other voltage-gated and ligand-gated Ca 2+ channels [10], indicating Ca 2+ entry directly through ASICs. The acidinduced increase of [Ca 2+ ] i is eliminated by specific and non-specific ASIC1a blockade, or by ASIC1 gene knockout [10,12]. Consistent with the finding of fluorescent imaging, acidactivated inward current is activated when extracellular solution contains Ca 2+ as the only conducting cation [10].…”

Section: Activation Of Asics Induces Membrane Depolarization and Incrmentioning

confidence: 70%

“…In one study, pH 0.5 of 6.8 has been demonstrated [23]. In addition to conducting Na + ions, homomeric ASIC1a channels are permeable to Ca 2+ ions [10,12,13]. ASIC1b (ASIC1β) is a splice variant of ASIC1a with restricted expression in sensory neurons [24].…”

Section: Tissue Distribution and Electrophysiological Properties Of Amentioning

confidence: 99%

“…For homomeric ASIC1a channels, acid activation also induces Ca 2+ entry directly through these channels [10,12,13]. In addition, the ASIC-mediated membrane depolarization may facilitate the activation of voltage-gated Ca 2+ channels and NMDA receptor-gated channels [22], further promoting neuronal excitation and [Ca 2+ ] i accumulation.…”

Section: Activation Of Asics Induces Membrane Depolarization and Incrmentioning

confidence: 99%

“…The Ca 2+ -permeability of ASICs in CNS neurons have been characterized using fluorescent Ca 2+ imaging and ion-substitution protocols [10,12]. In mouse cortical and hippocampal neurons, activation of ASICs by decreasing pH o induces increases of [Ca 2+ ] i .…”

Section: Activation Of Asics Induces Membrane Depolarization and Incrmentioning

confidence: 99%

“…For decades, the entity or receptor that detects pH o changes surrounding neurons and its signal transduction pathway remained elusive. The recent finding that a fall of pH o activates a distinct class of cation channels, the acid-sensing ion channels (ASICs), in peripheral sensory neurons and in the neurons of the central nervous system, dramatically changed the view of acid signaling and offered new pharmacological targets for neurological diseases [7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases

Xiong

Pignataro²,

et al. 2008

Current Opinion in Pharmacology

212

161

View full text Add to dashboard Cite

A significant drop of tissue pH or acidosis is a common feature of acute neurological conditions such as ischemic stroke, brain trauma, and epileptic seizures. Acid-sensing ion channels, or ASICs, are proton-gated cation channels widely expressed in peripheral sensory neurons and in the neurons of the central nervous system. Recent studies have demonstrated that activation of these channels by protons plays an important role in a variety of physiological and pathological processes such as nociception, mechanosensation, synaptic plasticity, and acidosis-mediated neuronal injury. This review provides an overview of the recent advance in electrophysiological, pharmacological characterization of ASICs, and their role in neurological diseases. Therapeutic potential of current available ASIC inhibitors is discussed.

show abstract

Section: Activation Of Asics Induces Membrane Depolarization and Incrmentioning

confidence: 70%

Section: Tissue Distribution and Electrophysiological Properties Of Amentioning

confidence: 99%

Section: Activation Of Asics Induces Membrane Depolarization and Incrmentioning

confidence: 99%

Section: Activation Of Asics Induces Membrane Depolarization and Incrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases

Xiong

Pignataro²,

et al. 2008

Current Opinion in Pharmacology

212

161

View full text Add to dashboard Cite

show abstract

Acid‐Sensing Ion Channels and Pain

Walder

Benson

Sluka

2009

Peripheral Receptor Targets for Analgesia

View full text Add to dashboard Cite

Acid‐Sensing Ion Channel 3 Deficiency Increases Inflammation but Decreases Pain Behavior in Murine Arthritis

Sluka

Rasmussen

Edgar

et al. 2013

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective Through its location on nociceptors, acid sensing ion channel 3 (ASIC3) is activated by decreases in pH and plays a significant role in musculoskeletal pain. We recently showed that decreases in pH activate ASIC3 located on fibroblast-like synoviocytes (FLS). Since FLS are key cells in the inflammatory process we tested if ASIC3-deficient mice with arthritis have altered inflammation and pain relative to controls. Methods Arthritis was induced by injection of a cocktail of anti-type II collagen antibodies induced collagen antibodyarthritis (CAIA). Inflammation and pain parameters in ASIC3−/− and ASIC3+/+ mice were assessed. Disease severity was measured with clinical arthritis scores, joint diameters, histological analysis of joints, and qPCR for synovial gene expression. Pain behaviors were measured by examining withdrawal thresholds of the joint and paw and by measuring physical activity levels in mice. Cell death was assessed with a Live/Dead assay in FLS in response to decreases in pH. Results Surprisingly, ASIC3−/− mice with CAIA demonstrated significantly increased joint inflammation, joint destruction and expression of IL-6, MMP-3 and MMP-13 in joint tissue compared to ASIC3+/+ mice. ASIC3+/+ FLS show enhanced cell death when exposed to pH 6.0 in the presence of interleukin-1β that is abolished in ASIC3−/− FLS. Despite enhanced disease severity, ASIC3−/− mice do not develop mechanical hypersensitivity of the paw and show greater levels of physical activity. Conclusion These data are consistent with the hypothesis that ASIC3 plays a protective role in inflammatory arthritis conditions by limiting inflammation through enhanced synoviocyte cell death to reduce disease severity and produce pain to reduce joint use.

show abstract

Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a

Abstract: Acid-sensing ion channel (ASIC

Cited by 345 publications

References 45 publications

Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases

Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases

Acid‐Sensing Ion Channels and Pain

Acid‐Sensing Ion Channel 3 Deficiency Increases Inflammation but Decreases Pain Behavior in Murine Arthritis

Contact Info

Product

Resources

About