Regulating quantal size of neurotransmitter release through a GPCR voltage sensor
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
Abstract
Significance The amount of neurotransmitter release triggered by Ca 2+ from a presynaptic single vesicle (quantal size, QS) is fundamental and determines the strength of synaptic transmission. The present study provides compelling evidence that the QS of catecholamine is increased by membrane depolarization per se (bypassing Ca 2+ ) via the voltage-sensitive ATP-GPCR/P2Y 12 in sympathetic chromaffin cells. D76-P2Y 12 and D127-P2Y 12 are revealed as the voltage-sensing sites by introducing two GPCR reporting systems. We also establish the physiology relevance of voltage dependence of catecholamine QS, offering a signaling pathway—Vm → P2Y 12 (D76/D127) → Giβγ → QS → myocyte contractility—for diverse functions in the nervous system and other systems containing GPCRs.