Intracellular Acidification Suppresses Synaptic Vesicle Mobilization in the Motor Nerve Terminals.

Area of Science:

• Neuroscience
• Cell Biology
• Physiology

Background:

• Intracellular protons regulate presynaptic processes, including synaptic vesicle and endosome function.
• Synaptic activity can cause transient intraterminal space acidification.
• The H+-pump is crucial for maintaining organelle acidification.

Purpose of the Study:

• To investigate the impact of intracellular acidification on presynaptic events governing neurotransmitter release.
• To elucidate the role of increased intracellular proton concentration ([H+]in) in regulating neurotransmission.

Main Methods:

• Utilized microelectrode recordings to measure postsynaptic responses as an indicator of neurotransmitter release.
• Employed the exo-endocytic marker FM1-43 to study synaptic vesicle dynamics.
• Induced intracellular acidification using propionate in mouse diaphragm and frog cutaneous pectoris neuromuscular junctions.

Main Results:

• Cytoplasmic acidification significantly reduced neurotransmitter release during the initial minute of high-frequency stimulation (20 Hz).
• Observed a decrease in FM1-43 loss during exocytosis, indicating reduced vesicle fusion with the plasma membrane.
• Synaptic vesicle endocytosis remained unaffected by acidification.
• Acidification blocked the enhancing effect of 24-hydroxycholesterol on synaptic vesicle mobilization.

Conclusions:

• Increased intracellular proton concentration ([H+]in) negatively regulates neurotransmission.
• This regulation occurs through the suppression of synaptic vesicle delivery to release sites during periods of high neuronal activity.
• The findings suggest a negative feedback loop mechanism for controlling neurotransmitter release.