Abstract
Acid-sensing ion channels (ASICs) have an important influence on human physiology and pathology. They are members of the degenerin/epithelial sodium channel family. Four genes encode at least six subunits, which combine to form a variety of homotrimers and heterotrimers. Of these, ASIC1a homotrimers and ASIC1a/2 heterotrimers are most widely expressed in the central nervous system (CNS). Investigations into the function of ASIC1a in the CNS have revealed a wealth of information, culminating in multiple contemporary reviews. The lesser-studied ASIC2 subunits are in need of examination. This review will focus on ASIC2 in health and disease, with discussions of its role in modulating ASIC function, synaptic targeting, cardiovascular responses, and pharmacology, while exploring evidence of its influence in pathologies such as ischemic brain injury, multiple sclerosis, epilepsy, migraines, drug addiction, etc. This information substantiates the ASIC2 protein as a potential therapeutic target for various neurological, psychological, and cerebrovascular diseases.
Highlights
Neurotransmission is the fundamental process through which neurons store and transfer information
In a study aimed to examine the brain-region-specific role of ASIC2, we found that ASIC2 deletion had no impact on acid-mediated responses in the cerebellum
Through in vivo investigations looking at the seizure behavior of negative control rats versus rats transfected with ASIC2a-expressing adeno-associated viruses, it was found that ASIC2a overexpression significantly accelerated the onset of the first seizure episode, reaching Racine stage IV and increased the occurrence of status epilepticus episodes that reached Racine stage IV [18]
Summary
Neurotransmission is the fundamental process through which neurons store and transfer information. ASIC2b does not conduct acid-activated inward-currents on its own, but it does affect the expression of ASIC1a [29] Due to this pH-insensitive property, one might conclude that ASIC2 has a comparatively minimal role in physiological or pathological activities. Relating to ASIC2, ASIC1a forms multimeric complexes with ASIC2 subunits and has its expression promoted by ASIC2 [9,10] These interactions suggest that ASIC2 may serve a modulatory role in synaptic plasticity [17,41]. The proton activation of ASIC1a leads to membrane depolarization and could assist in removing the Mg2+ ion block of NMDARs which, in turn, increases the probability of forming LTP and establishing synaptic plasticity [47]. To other ASIC subtypes, ASIC2 is implicated in normal fear physiology
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