Molecular Mechanism of Constitutive Endocytosis of Acid-Sensing Ion Channel 1a and Its Protective Function in Acidosis-Induced Neuronal Death
نویسندگان
چکیده
منابع مشابه
Molecular mechanism of constitutive endocytosis of Acid-sensing ion channel 1a and its protective function in acidosis-induced neuronal death.
Acid-sensing ion channels (ASICs) are proton-gated cation channels widely expressed in the peripheral and CNSs, which critically contribute to a variety of pathophysiological conditions that involve tissue acidosis, such as ischemic stroke and epileptic seizures. However, the trafficking mechanisms of ASICs and the related proteins remain largely unknown. Here, we demonstrate that ASIC1a, the m...
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Acid-sensing ion channel 1a (ASIC1a) promotes neuronal damage during pathological acidosis. ASIC1a undergoes a process called steady-state desensitization in which incremental pH reductions desensitize the channel and prevent activation when the threshold for acid-dependent activation is reached. We find that dynorphin A and big dynorphin limit steady-state desensitization of ASIC1a and acid-ac...
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Acid-sensing ion channel-1a (ASIC1a) is a potential therapeutic target for multiple neurological diseases. We studied here ASIC1a glycosylation and trafficking, two poorly understood processes pivotal in determining the functional outcome of an ion channel. We found that most ASIC1a in the mouse brain was fully glycosylated. Inhibiting glycosylation with tunicamycin reduced ASIC1a surface traff...
متن کاملExtracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a.
Acid-sensing ion channel (ASIC) 1a subunit is expressed in synapses of central neurons where it contributes to synaptic plasticity. However, whether these channels can conduct Ca(2+) and thereby raise the cytosolic Ca(2+) concentration, [Ca(2+)](c), and possibly alter neuronal physiology has been uncertain. We found that extracellular acidosis opened ASIC1a channels, which provided a pathway fo...
متن کاملAcid-sensing ion channel 1a regulates the survival of nucleus pulposus cells in the acidic environment of degenerated intervertebral discs
Objective(s): Activation of acid-sensing ion channel 1a (ASIC1a) is responsible for tissue injury caused by acidosis in nervous systems. But its physiological and pathological roles in nucleus pulposus cells (NPCs) are unclear. The aim of this study is to investigate whether ASIC1a regulates the survival of NPCs in the acidic environment of degenerated discs. Materials and Methods: NPCs were i...
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ژورنال
عنوان ژورنال: Journal of Neuroscience
سال: 2013
ISSN: 0270-6474,1529-2401
DOI: 10.1523/jneurosci.5206-12.2013