Stimulus-secretion coupling in neurohypophysial nerve endings: A role for intravesicular sodium?

It is generally accepted that Ca is essentially involved in regulated secretion, but the role of this cation, as well as others such as Na, is not well understood. ho illustrative example occurs in neurohypophysial secretion, where an experimentally induced increase in the cytosolic concentration of Na+ can induce continuous neuropeptide release. In contrast, an increase in cytosolic Ca2+ will have only a transient stimulatory effect The secretion-promoting targets for Ca2+ are not known; they may be cytosolic, as is usually assumed, but they mag. also be intravesicular, especially in view of evidence that Ca-rich secretory vesicles are preferentially secreted. In the present work, we have investigated the movements of these cations into and out of secretory vesicles during stimulus-secretion coupling. Isolated rat neurohypophysial nerve endings were stimulated by potassium (55 mM) depolarization, and at 6 min (peak secretion) and 20 min after the onset of stimulation, the elemental content of individual secretory vesicles was measured by quantitative x-ray microanalysis. A depolarization-induced transient increase in intravesicular Na+ concentration was found to coincide with the onset of secretion, Moreover, only a predicted small fraction of peripheral vesicles-presumably the docked ones-vr-ere Nat-loaded. The low sulfur concentration of Na+-rich resides most likely resulted from vesicle swelling. The results suggest that high intravesicular Na+ concentrations in docked vesicles, occurring by Na+/Ca2+ exchange or by transient fusion pore opening, is a proximal event in exocytosis.