The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.
Wemmie JA,
Chen J,
Askwith CC,
Hruska-Hageman AM,
Price MP,
Nolan BC,
Yoder PG,
Lamani E,
Hoshi T,
Freeman JH Jr,
Welsh MJ.
Department of Psychiatry, University of Iowa, Iowa City, IA 52242, USA.
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.
PMID: 11988176 [PubMed - indexed for MEDLINE]