Single-Vesicle Electrochemistry Reveals Polysaccharide from Glochidion eriocarpum Champ. Regulates Vesicular Storage and Exocytotic Release of Dopamine

Polysaccharides, which are well-known natural macromolecules, have been recognized for their protective effects on neurons and their influence on extracellular dopamine levels in the brain. It is crucial to investigate the impact of plant polysaccharides on neurotransmission, particularly regarding the vesicular storage and exocytosis of neurotransmitters. In this study, we demonstrated the possibility of studying how the polysaccharide from Glochidion eriocarpum Champ.(GPS) affects vesicle dopamine content and the dynamics of exocytosis in pheochromocytoma (PC12) cells using single-cell amperometry (SCA) and intracellular vesicle impact electrochemical cytometry (IVIEC). Our results unambiguously demonstrate that GPS effectively enhances vesicular neurotransmitter content and alters the dynamics of exocytosis, favoring a smaller fraction of content released in exocytotic release, thereby inducing the partial release mode. These significant effects are attributed to GPS's efficient elevation of calcium influx, significant alteration in the composition of exocytosis-related membrane lipids, and enhancement of free radical scavenging ability. These findings not only establish GPS as a promising candidate for preventive or therapeutic interventions against neurodegenerative disorders but also reiterate the importance of screening native neurologic drugs with single-vesicle electrochemical approaches, the combination of SCA and IVIEC, from a neurotransmitter-centric perspective.