Synaptic signals mediated by protons and acid-sensing ion channels
Osvaldo D Uchitel1, Carlota González Inchauspe1, Carina Weissmann1
1Departamento de Fisiología, Biología Molecular y Celular "Dr. Héctor Maldonado", Facultad de Ciencias Exactas y Naturales, Instituto de Fisiología, Biología molecular y Neurociencias (IFIBYNE) CONICET, Universidad de Buenos Aires, Ciudad Universitaria, (C1428EGA), Ciudad Autónoma de Buenos Aires, Argentina.
Synapse (New York, N.Y.)
|June 11, 2019
Summary
Protons act as neurotransmitters, signaling through acid-sensing ion channels (ASICs) in the brain. These channels influence neuronal communication, synaptic plasticity, and behaviors, offering potential therapeutic targets.
Area of Science:
- Neuroscience
- Molecular Biology
- Neuropharmacology
Background:
- Extracellular pH fluctuations serve as critical signals in neuronal communication, particularly within the synaptic cleft during neurotransmission.
- Protons are increasingly recognized as neurotransmitters, modulating neuronal activity in key central nervous system (CNS) regions like the amygdala, nucleus accumbens, and brainstem.
- Acid-sensing ion channels (ASICs) are activated by protons, influencing synaptic transmission and neuronal function.
Purpose of the Study:
- To elucidate the role of protons and ASICs in synaptic transmission and neuronal communication.
- To investigate the involvement of ASICs in synaptic plasticity, learning, memory, and behavior.
- To explore endogenous modulators of ASICs and their potential for therapeutic development.
Main Methods:
- Investigated proton signaling in synaptic transmission.
- Examined the function of acid-sensing ion channels (ASICs) in the central nervous system.
- Utilized pharmacological and genetic inhibition of ASIC1a to assess behavioral and cognitive effects.
- Identified endogenous molecules that modulate ASIC activity.
Main Results:
- Protons are released during nerve stimulation and activate postsynaptic ASICs.
- Calcium (Ca2+) influx through certain ASICs contributes to synaptic plasticity.
- Inhibition of ASIC1a impairs learning, memory, fear, and cocaine-seeking behaviors.
- Various endogenous molecules (e.g., arachidonic acid, histamine, lactate) modulate ASIC function.
Conclusions:
- Protons play a significant role as neurotransmitters, impacting neuronal communication and CNS function.
- ASICs are crucial for synaptic plasticity and are implicated in learning, memory, and motivated behaviors.
- Endogenous modulators of ASICs suggest complex synaptic modulation mechanisms.
- ASICs represent promising targets for novel pharmacological therapies.
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