Synaptic signals mediated by protons and acid‐sensing ion channels

Abstract

Extracellular pH changes may constitute significant signals for neuronal communication. During synaptic transmission, changes in pH in the synaptic cleft take place. Its role in the regulation of presynaptic Ca2+ currents through multivesicular release in ribbon‐type synapses is a proven phenomenon. In recent years, protons have been recognized as neurotransmitters that participate in neuronal communication in synapses of several regions of the CNS such as amygdala, nucleus accumbens, and brainstem. Protons are released by nerve stimulation and activate postsynaptic acid‐sensing ion channels (ASICs). Several types of ASIC channels are expressed in the peripheral and central nervous system. The influx of Ca2+ through some subtypes of ASICs, as a result of synaptic transmission, agrees with the participation of ASICs in synaptic plasticity. Pharmacological and genetical inhibition of ASIC1a results in alterations in learning, memory, and phenomena like fear and cocaine‐seeking behavior. The recognition of endogenous molecules, such as arachidonic acid, cytokines, histamine, spermine, lactate, and neuropeptides, capable of inhibiting or potentiating ASICs suggests the existence of mechanisms of synaptic modulation that have not yet been fully identified and that could be tuned by new emerging pharmacological compounds with potential therapeutic benefits.

Enriched environment remedies cognitive dysfunctions and synaptic plasticity through NMDAR-Ca2+-Activin A circuit in chronic cerebral hypoperfusion rats

“…The Ca 2+ signal induced by synaptic activity and transmitted to the nucleus is the primary pathway for synapses to communicate with the nucleus. Synaptic stimulation upregulates Ca 2+ levels in neurons through NMDAR and initiates downstream AID gene expression, improving individual learning and memory capabilities through synaptic plasticity mechanisms [ 16 , 17 ]. ActA increases the postsynaptic influx of Ca 2+ in hippocampal neurons and participates in the regulation of synaptic plasticity through promoting the phosphorylation of NMDAR [ 18 , 19 ].…”

Topography and motion of acid-sensing ion channel intracellular domains

“…The predominant sensor of extracellular pH in the central and peripheral nervous system is thought to be acid-sensing ion channels (ASICs) ( Pattison et al, 2019 ). This family of trimeric pH-activated sodium-selective ion channels couples extracellular acidification to numerous physiological and pathophysiological consequences including synaptic transmission and plasticity ( Du et al, 2014 ; Kreple et al, 2014 ; Liu et al, 2016 ; Uchitel et al, 2019 ; Yu et al, 2018 ), fear memory consolidation and expression ( Du et al, 2017 ; Taugher et al, 2020 ; Taugher et al, 2017 ; Taugher et al, 2014 ), epilepsy ( Ziemann et al, 2008 ), and ischemia-induced cell death ( Wemmie et al, 2013 ; Xiong et al, 2004 ). However, in many of these cases, the duration of extracellular acidosis is quite long.…”

The role of nociceptin in opioid regulation of brain functions

“…В центральной нервной системе описано, по крайней мере, три субъединицы из шести (ASIC1a, ASIC2a и ASIC2b) [20]. Установлено, что ASIC1а и ASIC2 локализуются в постсинаптической мембране и телах нейронов и принимают непосредственное участие в процессах синаптической пластичности, обучении, передаче нервного возбуждения, а также при патологических состояниях -ишемических процессах и эпилепсии [20,21]…”