Regulating Quantal Size of Neurotransmitter Release Through a GPCR Voltage Sensor

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2020 Oct 13

PMID 33046653

Citations 10

Authors

Quanfeng Zhang

Bing Liu

Yinglin Li

Lili Yin

Muhammad Younus

Xiaohan Jiang

Zhaohan Lin

Xiaoxuan Sun

Rong Huang

Bin Liu

Qihui Wu

Feipeng Zhu

Zhuan Zhou

Affiliations

Soon will be listed here.

Abstract

Current models emphasize that membrane voltage (Vm) depolarization-induced Ca 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, 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 receptors. D76 and D127 in P2Y 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(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.

Citing Articles

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