Rong Huang1,2 · Xingyu Du1  · Qihui Wu1,3 · Yuan Wang1  · Yuqi Hang1  · Xi Wu1  · Yiman Li1  · Jie Li1  · Zhongjun Qiao1  · Yinglin Li1  · Lili Yin1  · Xiaoxuan Sun1  · Bing Liu1  · Feipeng Zhu1  · Quanfeng Zhang1  · Changhe Wang2,4 · Zuying Chai1,5 · Zhuan Zhou1

1 State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology and Peking‑Tsinghua Center for Life Sciences and PKU‑IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China 

2 Department of Neurology, the First Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China 

3 Shangai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain‑Like Intelligence, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China 

4 Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China 

5 School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China

Abstract

While Katz’s Ca²⁺ hypothesis has defined that action potentials trigger neurotransmitter release through Ca²⁺-dependent secretion (CDS), recent discoveries of Ca²⁺-independent secretion (CiVDS) have demonstrated that action potentials per se can directly trigger exocytosis independent of Ca²⁺. However, a critical gap remains regarding how CDS and CiVDS coordinate to precisely control neurotransmitter release within a single neuron’s soma and axons/terminals. Here, using high-resolution live imaging, we simultaneously visualized single-vesicle release in the somata and axons/terminals of individual dorsal root ganglion (DRG) neurons and show that: (1) CiVDS and CDS co-exist in both somatic and axonal regions; (2) the release probability of CiVDS in axons is ~2-fold higher than in somata; (3) CiVDS accounts for > 60% of total axonal release; (4) CiVDS favors full fusion-like quantal release while CDS favors kiss-and-run sub-quantal release. These findings suggest a more profound contribution of CiVDS than CDS in axonal neurotransmission in sensory DRG neurons.

Keywords

Ca²⁺-independent secretion; Ca²⁺-dependent secretion; Single vesicle release; Release modes; Dorsal root ganglion neurons

[SpringerLink]