Abstract
Many central neurons possess large acid-activated currents, yet their molecular identity is unknown. We found that eliminating the acid sensing ion channel (ASIC) abolished H(+)-gated currents in hippocampal neurons. Neuronal H(+)-gated currents and transient acidification are proposed to play a role in synaptic transmission. Investigating this possibility, we found ASIC in hippocampus, in synaptosomes, and in dendrites localized at synapses. Moreover, loss of ASIC impaired hippocampal long-term potentiation. ASIC null mice had reduced excitatory postsynaptic potentials and NMDA receptor activation during high-frequency stimulation. Consistent with these findings, null mice displayed defective spatial learning and eyeblink conditioning. These results identify ASIC as a key component of acid-activated currents and implicate these currents in processes underlying synaptic plasticity, learning, and memory.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acid Sensing Ion Channels
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Animals
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Conditioning, Eyelid
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials
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Hippocampus / cytology
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Hippocampus / metabolism
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Hydrogen-Ion Concentration
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In Vitro Techniques
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Kynurenic Acid / pharmacology
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Learning / physiology*
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Long-Term Potentiation / physiology
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Membrane Proteins*
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Memory / physiology*
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Mice
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Mice, Knockout
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Nerve Tissue Proteins / metabolism
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Neuronal Plasticity / physiology*
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Neurons / drug effects
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Neurons / metabolism*
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Patch-Clamp Techniques
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Proteins / metabolism*
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Rats
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Sodium Channels / genetics
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Sodium Channels / metabolism*
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Synaptic Transmission / physiology
Substances
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ASIC3 protein, human
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Acid Sensing Ion Channels
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Excitatory Amino Acid Antagonists
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Membrane Proteins
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Nerve Tissue Proteins
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Proteins
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Sodium Channels
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postsynaptic density proteins
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Kynurenic Acid