1. Intracellular Acidification Suppresses Synaptic Vesicle Mobilization in the Motor Nerve Terminals
- Author
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A. V. Zakharov, U. O. Odnoshivkina, Alexey M. Petrov, Kamilla A. Mukhutdinova, R. D. Mukhametzyanov, and Andrey L. Zefirov
- Subjects
0301 basic medicine ,Endocytic cycle ,Neurotransmission ,Biochemistry ,Synaptic vesicle ,Exocytosis ,Neuromuscular junction ,acidification ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,neurotransmission ,Neurotransmitter ,Molecular Biology ,Synaptic vesicle endocytosis ,neuromuscular junction ,synaptic vesicle translocation ,Synaptic vesicle exocytosis ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Biophysics ,Molecular Medicine ,exocytosis ,030217 neurology & neurosurgery ,Research Article ,Biotechnology - Abstract
Intracellular protons play a special role in the regulation of presynaptic processes, since the functioning of synaptic vesicles and endosomes depends on their acidification by the H+-pump. Furthermore, transient acidification of the intraterminal space occurs during synaptic activity. Using microelectrode recording of postsynaptic responses (an indicator of neurotransmitter release) and exo-endocytic marker FM1-43, we studied the effects of intracellular acidification with propionate on the presynaptic events underlying neurotransmitter release. Cytoplasmic acidification led to a marked decrease in neurotransmitter release during the first minute of a 20-Hz stimulation in the neuromuscular junctions of mouse diaphragm and frog cutaneous pectoris muscle. This was accompanied by a reduction in the FM1-43 loss during synaptic vesicle exocytosis in response to the stimulation. Estimation of the endocytic uptake of FM1-43 showed no disruption in synaptic vesicle endocytosis. Acidification completely prevented the action of the cell-membrane permeable compound 24-hydroxycholesterol, which can enhance synaptic vesicle mobilization. Thus, the obtained results suggest that an increase in [H+]in negatively regulates neurotransmission due to the suppression of synaptic vesicle delivery to the sites of exocytosis at high activity. This mechanism can be a part of the negative feedback loop in regulating neurotransmitter release.
- Published
- 2020