Wei Lisi, Wang Xin, Sun Min, Shin Wonchul, Gillis Kevin D, Wu Ling-Gang
National Institute of Neurological Disorders and Stroke, 35 Convent Dr., Bldg. 35, Bethesda, MD 20892, USA.
Department of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65201, USA.
Biophys Rep (N Y). 2025 Jun 11;5(2):100212. doi: 10.1016/j.bpr.2025.100212. Epub 2025 May 7.
Exocytosis, which mediates important functions like synaptic transmission and stress responses, has been postulated to release all transmitter molecules in the vesicle in the "all-or-none" quantal hypothesis. Challenging this hypothesis, amperometric current recordings of catecholamine release propose that sub-quantal or partial transmitter release is dominant in various cell types, particularly chromaffin cells. The sub-quantal hypothesis predicts that fusion pore closure (kiss-and-run fusion), the cause of sub-quantal release, is dominant, and blocking pore closure increases quantal size. We tested these predictions by imaging fusion pore closure and amperometric recording of catecholamine release in chromaffin cells during high potassium application, the most-used stimulation protocol for sub-quantal release study. We found that fusion pore closure is not predominant, and inhibition of the fusion pore closure does not increase the quantal size calculated from the amperometric current charge when a sufficiently long integration time is used. These results suggest that sub-quantal release is not prevalent during high potassium application in adrenal chromaffin cells.
胞吐作用介导诸如突触传递和应激反应等重要功能，在“全或无”量子假说中，它被假定为释放囊泡中的所有递质分子。对这一假说提出挑战的是，儿茶酚胺释放的安培电流记录表明亚量子或部分递质释放在各种细胞类型中占主导地位，尤其是嗜铬细胞。亚量子假说预测，作为亚量子释放原因的融合孔关闭（即吻-跑融合）占主导地位，而阻断孔关闭会增加量子大小。我们通过在高钾应用期间对嗜铬细胞中的融合孔关闭进行成像以及对儿茶酚胺释放进行安培记录来检验这些预测，高钾应用是亚量子释放研究中最常用的刺激方案。我们发现融合孔关闭并非占主导地位，并且当使用足够长的积分时间时，融合孔关闭的抑制并不会增加根据安培电流电荷计算出的量子大小。这些结果表明，在肾上腺嗜铬细胞的高钾应用期间，亚量子释放并不普遍。
