BBB seminar: Erwin Neher
Control of neurotransmitter and hormone release by Ca++ and cAMP
Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
It has been known since the work of Katz and collaborators in the early 50s, 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 cAMP, modulate the release of both neurotransmitters and hormones. However, regulated secretion is a multistep process and the signaling pathways involved act at many stages. Biochemical and traditional electrophysiological techniques very often cannot dissociate between signaling actions on ion channels, vesicle trafficking and the secretory process itself. We have tried 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), which would allow to study secretion in single cells under voltage clamp conditions. This enabled one to clearly distinguish between influences on electrical signaling from those on the process of vesicle recruitment and on the process of exocytosis. We focus in our study on the role of [Ca++] and cAMP.
Professor Erwin Neher shares the Nobel Prize in Physiology or Medicine 1991 with Professor Bert Sakmann. The two German scientists earned this award for their discoveries concerning the function of single ion channels in cells. Their collaboration began in Göttingen in 1973, focusing on different subtypes of acetylcholine activated channels, and their first single channel records were published in 1976. As a consequence, each of them received a "Young Investigator Laboratory", making it possible for them, at that time in their early 30s, to attract a number of excellent postdoctoral fellows and to continue their fruitful collaboration, refining their ingenious patch-clamp technique for single channel recordings. While Bert Sakmann eventually moved on to apply molecular biology techniques to problems of ion channel physiology, Erwin Neher shifted his interest away from the channels themselves and over to processes initiated by ion channel activity inside cells. He developed this line of research into the details of secretion of hormones and neurotransmitters, focusing on Ca2+-dependent mechanisms. For many of these problems the bovine adrenomedullary chromaffin cells have served as a model, for others specific synapses such as the Calyx of Held. The recruitment of releasable vesicle pools to the site of exocytosis is but one of the ongoing problems under investigation, employing fluorescent fusion proteins as probes.
In his lecture Professor Neher will bring us upfront on the current concepts of the cellular mechanisms for neurotransmission.