Acid-sensing ion channel 1a drives AMPA receptor plasticity following ischaemia and acidosis in hippocampal CA1 neurons

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Acid‐sensing ion channel 1a drives AMPA receptor plasticity following ischaemia and acidosis in hippocampal CA1 neurons

KEY POINTS The hippocampal CA1 region is highly vulnerable to ischaemic stroke. Two forms of AMPA receptor (AMPAR) plasticity - an anoxic form of long-term potentiation and a delayed increase in Ca(2+) -permeable (CP) AMPARs - contribute to this susceptibility by increasing excitotoxicity. In CA1, the acid-sensing ion channel 1a (ASIC1a) is known to facilitate LTP and contribute to ischaemic ac...

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N-glycosylation of acid-sensing ion channel 1a regulates its trafficking and acidosis-induced spine remodeling.

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...

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Dynorphin opioid peptides enhance acid-sensing ion channel 1a activity and acidosis-induced neuronal death.

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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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 is not required for normal hippocampal LTP and spatial memory.

Acid-sensing ion channel-1a (ASIC1a) is localized in brain regions with high synaptic density and is thought to contribute to synaptic plasticity, learning, and memory. A prominent hypothesis is that activation of postsynaptic ASICs promotes depolarization, thereby augmenting N-methyl-d-aspartate receptor function and contributing to the induction of long-term potentiation (LTP). However, evide...

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ژورنال

عنوان ژورنال: The Journal of Physiology

سال: 2015

ISSN: 0022-3751

DOI: 10.1113/jp270701