Neher_2006_Pflugers.Arch_453_261

It has been known since the work of Katz and collaborators in the early 1950s that an increase in intracellular Ca(++) concentration ([Ca(++)]) is the immediate trigger for neurotransmitter release. Later work has shown that, next to Ca(++), many other signaling pathways, particularly via cyclic AMP, modulate the release of both neurotransmitters and hormones. However, regulated secretion is a multistep process and the signaling mechanisms involved act at many stages. Biochemical and traditional electrophysiological techniques very often cannot distinguish whether a change in secretion is caused by regulation of ion channels, vesicle trafficking, or the exocytic process itself. My laboratory has made an effort to dissect the stimulus secretion pathway by developing assays in chromaffin cells (for catecholamine release) and at a glutamatergic central nervous synapse (the calyx of Held, a component of the auditory pathway), which permit the study of secretion in single cells under voltage clamp conditions. This enables us to clearly distinguish between consequences of changes in electrical signaling, from those regarding the process of vesicle recruitment or the process of exocytosis.