The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.
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.
Wemmie
John A
JA
Department of Psychiatry, University of Iowa, Iowa City, IA 52242, USA.
Chen
Jianguo
J
Askwith
Candice C
CC
Hruska-Hageman
Alesia M
AM
Price
Margaret P
MP
Nolan
Brian C
BC
Yoder
Patrick G
PG
Lamani
Ejvis
E
Hoshi
Toshinori
T
Freeman
John H
JH
Welsh
Michael J
MJ
D062565:Acid Sensing Ion Channels; D000818:Animals; D003215:Conditioning, Eyelid; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D008565:Membrane Proteins; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
C112231:ASIC3 protein, human; D062565:Acid Sensing Ion Channels; D018691:Excitatory Amino Acid Antagonists; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D015222:Sodium Channels; C033652:postsynaptic density proteins; D007736:Kynurenic Acid