L-type Ca 2+ channels mediate regulation of glutamate release by subthreshold potential changes
| Autor: | Byoung Ju Lee, Unghwi Lee, Seung Hyun Ryu, Sukmin Han, Seung Yeon Lee, Jae Sung Lee, Anes Ju, Sunghoe Chang, Suk-Ho Lee, Sung Hyun Kim, Won-Kyung Ho |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Proceedings of the National Academy of Sciences. 120 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2220649120 |
| Popis: | Subthreshold depolarization enhances neurotransmitter release evoked by action potentials and plays a key role in modulating synaptic transmission by combining analog and digital signals. This process is known to be Ca 2+ dependent. However, the underlying mechanism of how small changes in basal Ca 2+ caused by subthreshold depolarization can regulate transmitter release triggered by a large increase in local Ca 2+ is not well understood. This study aimed to investigate the source and signaling mechanisms of Ca 2+ that couple subthreshold depolarization with the enhancement of glutamate release in hippocampal cultures and CA3 pyramidal neurons. Subthreshold depolarization increased presynaptic Ca 2+ levels, the frequency of spontaneous release, and the amplitude of evoked release, all of which were abolished by blocking L-type Ca 2+ channels. A high concentration of intracellular Ca 2+ buffer or blockade of calmodulin abolished depolarization-induced increases in transmitter release. Estimation of the readily releasable pool size using hypertonic sucrose showed depolarization-induced increases in readily releasable pool size, and this increase was abolished by the blockade of calmodulin. Our results provide mechanistic insights into the modulation of transmitter release by subthreshold potential change and highlight the role of L-type Ca 2+ channels in coupling subthreshold depolarization to the activation of Ca 2+ -dependent signaling molecules that regulate transmitter release. |
| Databáze: | OpenAIRE |
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