The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory

Neuron. 2002 Apr 25;34(3):463-77. doi: 10.1016/s0896-6273(02)00661-x.


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

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acid Sensing Ion Channels
  • Animals
  • Conditioning, Eyelid
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Kynurenic Acid / pharmacology
  • Learning / physiology*
  • Long-Term Potentiation / physiology
  • Membrane Proteins*
  • Memory / physiology*
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity / physiology*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Proteins / metabolism*
  • Rats
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Synaptic Transmission / physiology


  • ASIC3 protein, human
  • Acid Sensing Ion Channels
  • Excitatory Amino Acid Antagonists
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Proteins
  • Sodium Channels
  • postsynaptic density proteins
  • Kynurenic Acid