Title:Acid-Sensing Ion Channels: Focus on Physiological and Some Pathological Roles in the Brain
Volume: 19
Issue: 9
Author(s): Maksim Storozhuk*, Andrii Cherninskyi, Oleksandr Maximyuk, Dmytro Isaev and Oleg Krishtal
Affiliation:
- Department of Cellular Membranology, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, 4 Bogomoletz Street, Kyiv 01024,Ukraine
Abstract: Acid-sensing ion channels (ASICs) are Na+-permeable ion channels activated by protons
and predominantly expressed in the nervous system. ASICs act as pH sensors leading to neuronal excitation.
At least eight different ASIC subunits (including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3,
ASIC4, ASIC5) are encoded by five genes (ASIC1-ASIC5). Functional ASICs assembled in the plasma
membrane are homo- or heteromeric trimers. ASIC1a-containing trimers are of particular interest
as, in addition to sodium ions, they also conduct calcium ions and thus can trigger or regulate multiple
cellular processes. ASICs are widely but differentially expressed in the central and peripheral nervous
systems. In the mammalian brain, a majority of neurons express at least one ASIC subunit. Several recent
reviews have summarized findings of the role of ASICs in the peripheral nervous system, particularly
in nociception and proprioception, and the structure-function relationship of ASICs. However,
there is little coverage on recent findings regarding the role of ASICs in the brain. Here we review and
discuss evidence regarding the roles of ASICs: (i) as postsynaptic receptors activated by protons coreleased
with glutamate at glutamatergic synapses; (ii) as modulators of synaptic transmission at glutamatergic
synapses and GABAergic synapses; (iii) in synaptic plasticity, memory and learning; (iv) in
some pathologies such as epilepsy, mood disorders and Alzheimer's disease.
