Dorsal Root Ganglion Cells To Stimulate Secretion Coupling And Membrane Homeostasis

Action potential (AP) is a very important physiological signal in excitable cells including neurons and neuroendocrine cells. It is widely accepted that AP depolarize the plasma membrane and open voltage-dependent calcium channels (VDCCs), the calcium influx through VDCCs trigger the fusion of vesicles with plasma membrane and subsequent transmitter release. This fusion event is assumed as a strictly Ca2+-regulated process, and plays important roles in transmitter release, synaptic transmission and et al. Combined capacitance measurement, amperometric recording and optical detection of secretion, we want to address the question that if AP play some additional role (s) in the exocytosis process except only opening VDCCs.The main results obtained are listed below:1) We found depolarization of plasma membrane induced vesicle fusion and transmitter release (CIVDS) without the involvement of calcium in rat DRG neurons, but not in adrenal chromaffin cells. From the amperometric results obtained in chromaffin cells, we also found that the membrane potential might modulate the fusion process.2) We found following CIVDS rapid endocytosis occurred to retrieve the added membrane. This process was Ca2+-independnet, and modulated by activity. The activity-dependence of endocytosis was partially through some unknown phosphorylation process related to PKA pathway.We here describe a novel mechanism for plasma membrane insertion3) of delta-opioid receptor (DOR). Activation of the surface DORs causes a slow Ca2+ elevation by both inositol 1, 4, 5-trisphosphate receptor-mediated intracellular Ca2+ release and extracellular Ca2+ entry, resulting in a slow and long-lasting increase in intracellular Ca2+, exocytosis, DOR insertion and CGRP release. These findings suggest that DOR mediates a distinct positive-feedback mechanism to determine DOR insertion that is coupled with neuropeptide release, and thus reveal an unexpected function for one of the opioid receptors.Taken together, our results demonstrated that APs play some important roles in stimulus-secretion coupling. The depolarization of membrane induces secretion directly without Ca involvement in DRG neurons. These results help to understand the roles of APs in the stimulus-secretion process, and will also imply that membrane depolarization, as a natural signal in neurons, might has some direct roles in the cellular process except just as a trigger for channels.