Open AccessRegulating quantal size of neurotransmitter release through a GPCR voltage sensor
Author(s) -
Quanfeng Zhang,
Bing Liu,
Yinglin Li,
Lili Yin,
Muhammad Younus,
Xiaohan Jiang,
Ziyin Lin,
Xiaoxuan Sun,
Rong Huang,
Bin Liu,
Qihui Wu,
Feipeng Zhu,
Zhuan Zhou
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2005274117
Subject(s) - neurotransmitter , neurotransmission , depolarization , catecholamine , g protein coupled receptor , biology , biophysics , synaptic vesicle , microbiology and biotechnology , neuroscience , chemistry , vesicle , signal transduction , biochemistry , receptor , central nervous system , membrane
Current models emphasize that membrane voltage (Vm) depolarization-induced Ca 2+ influx triggers the fusion of vesicles to the plasma membrane. In sympathetic adrenal chromaffin cells, activation of a variety of G protein coupled receptors (GPCRs) can inhibit quantal size (QS) through the direct interaction of G protein Giβγ subunits with exocytosis fusion proteins. Here we report that, independently from Ca 2+ , Vm (action potential) per se regulates the amount of catecholamine released from each vesicle, the QS. The Vm regulation of QS was through ATP-activated GPCR-P2Y 12 receptors. D76 and D127 in P2Y 12 were the voltage-sensing sites. Finally, we revealed the relevance of the Vm dependence of QS for tuning autoinhibition and target cell functions. Together, membrane voltage per se increases the quantal size of dense-core vesicle release of catecholamine via Vm → P2Y 12 (D76/D127) → Giβγ → QS → myocyte contractility, offering a universal Vm-GPCR signaling pathway for its functions in the nervous system and other systems containing GPCRs.