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<p>While Katz’s Ca<sup>2+</sup> hypothesis has defined that action potentials trigger neurotransmitter release through Ca<sup>2+</sup>-dependent secretion (CDS), recent discoveries of Ca<sup>2+</sup>-independent secretion (CiVDS) have demonstrated that action potentials per se can directly trigger exocytosis independent of Ca<sup>2+</sup>. 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 &gt; 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.</p>

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Ca2+-Independent Exocytosis Favors Axonal Release through Enlarged Fusion Pores in Sensory Neurons

  • 期刊论文

  • 发表日期：

    2026年2月26日

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  • Rong Huang,
  • Xingyu Du,
  • Qihui Wu,
  • Yuan Wang,
  • Yuqi Hang,
  • Xi Wu,
  • Yiman Li,
  • Jie Li,
  • Zhongjun Qiao,
  • Yinglin Li,
  • Lili Yin,
  • Xiaoxuan Sun,
  • Bing Liu,
  • Feipeng Zhu,
  • Quanfeng Zhang,
  • Changhe Wang,
  • Zuying Chai,
  • Zhuan Zhou

摘要

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.