突触前囊泡分泌的神经递质数量决定突触后信号传导的强度。经典Katz学说认为囊泡分泌都是量子化“全或无”模式。我室1995年首次发现交感系统肾上腺嗜铬细胞存在亚量子化“sub-quantal”分泌模式，证明单个囊泡分泌具有可塑性。我和同事最近发现亚量子分泌与量子分泌可以共存，并受GPCR-Giβγ和动力蛋白dynamin调控（Neuron，2019；J Neurosci，2019）。最近预实验发现：dynamin敲除后，Giβγ不再对囊泡的亚量子化分泌产生调控作用，提示dynamin参与Giβγ的下游信号通路。本申请将使用我室优势的单囊泡电化学和TIRF成像，在嗜铬细胞上研究（1）dynamin 1调控囊泡亚量子化分泌的分子机理；（2）dynamin 1调控的单个囊泡中肾上腺素分泌对外周心血管系统的生理作用。该研究提出单个囊泡可塑性的分子机理，并进一步增强我室在亚量子化分泌领域的优势地位。

The number of neurotransmitters released from presynaptic vesicles determines the strength of postsynaptic transmission. Sixty-four years ago, Bernard Katz proposed that presynaptic transmission is mediated as “all-or-none” neurotransmitter release. Until recently, this quantal hypothesis has been one of the central concepts in synaptic transmission. In 1995, the first subquantal release mode was found in the sympathetic adrenal chromaffin cells, suggesting that plasticity occurs on the level of single vesicle release. My colleagues and I recently discovered that subquantal and quantal release can coexist in chromaffin cells and are regulated by GPCR-Giβγ and dynamin (Neuron, 2019; J Neurosci, 2019). Recent pre-experiments found that after dynamin is knocked out, Giβγ no longer regulates the subquantal release of vesicles, suggesting that dynamin is involved in the downstream signaling pathway of Giβγ. This application will use our superior single vesicle electrochemical and TIRF imaging methods to study (1) the molecular mechanism of dynamin 1 regulating vesicle subquantal release in chromaffin cells; (2) physiological effects of epinephrine secretion regulated by dynamin 1 on the peripheral cardiovascular system. This research proposes the molecular mechanism of single vesicle plasticity, and further strengthens our laboratory's dominant position in the vesicle subquantal release field.