MECHANISMS OF HORMONE AND TRANSMITTER SECRETION

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Our recent work has focussed on the processes leading to fusion between granule and plasma membranes during exocytosis in cells such as chromaffin cells, beta cells in islets of Langerhans, frog neuromuscular junction, and tracheal submucosal gland cells. Synexin, a calcium binding membrane fusion protein found in many tissues, was found to fuse membranes by a mechanism involving membrane mixing occurring prior to volume mixing. Synexin was also found to enter membranes and change the capacitance, and simultaneously to exhibit calcium channel activity. From these and other data we have formulated a hydrophobic bridge hypothesis for membrane fusion driven by synexin. The fast-freeze electron microscopy technique has been used to measure changes in distribution of elements and their concentrations in discrete regions of cytosol alkalinization of chromaffin granules suppresses secretion, implicating the state of the granule interior in the exocytosis process. Metalloendoprotease inhibitors block secretions by accelerating calcium efflux. Calcium enters chromaffin cells through a variety of voltage sensitive calcium channels, including at least one that is insensitive to dihydro- pyridines or w-conotoxin. In islet of Langerhans, fetal B-cells have functional ATP blockable channels, but still respond poorly to glucose. Cyclic Amp may potentiate insulin secretion by enhancing coupling between cells. Potassium channels from internal organelles of nerve endings can be reconstituted using a patch pipet technique.