Synaptic signals mediated by protons and acid-sensing ion channels

CARINA WEISSMANN; CARLOTA GONZÁLEZ INCHAUSPE; CARINA WEISSMANN; CARLOTA GONZÁLEZ INCHAUSPE; OSVALDO D. UCHITEL ; OSVALDO D. UCHITEL

SYNAPSE

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2019 vol. 73 p. 22120 - 22140

0887-4476

Extracellular pH changes may constitute significant signals for neuronal communication.During synaptic transmission, changes in pH in the synaptic cleft take place. Its role inthe regulation of presynaptic Ca2+ currents through multivesicular release in ribbon‐typesynapses is a proven phenomenon. In recent years, protons have been recognized asneurotransmitters that participate in neuronal communication in synapses of several regionsof the CNS such as amygdala, nucleus accumbens, and brainstem. Protons are releasedby 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 andgenetical inhibition of ASIC1a results in alterations in learning, memory, and phenomenalike fear and cocaine‐seeking behavior. The recognition of endogenous molecules, suchas arachidonic acid, cytokines, histamine, spermine, lactate, and neuropeptides, capableof inhibiting or potentiating ASICs suggests the existence of mechanisms of synapticmodulation that have not yet been fully identified and that could be tuned by newemerging pharmacological compounds with potential therapeutic benefits.