Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a
نویسندگان
چکیده
منابع مشابه
Extracellular 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...
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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...
متن کاملMolecular 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) 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 chloride modulates the desensitization kinetics of acid-sensing ion channel 1a (ASIC1a).
Acid-sensing ion channels (ASICs) are sodium channels gated by extracellular protons. The recent crystallization of ASIC1a identified potential binding sites for Cl(-) in the extracellular domain that are highly conserved between ASIC isoforms. However, the significance of Cl(-) binding is unknown. We investigated the effect of Cl(-) substitution on heterologously expressed ASIC1a current and H...
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ژورنال
عنوان ژورنال: Proceedings of the National Academy of Sciences
سال: 2004
ISSN: 0027-8424,1091-6490
DOI: 10.1073/pnas.0308636100