Large and rapid changes in light scattering accompany secretion from nerve terminals of the mammalian neurohypophysis (posterior pituitary). In the mouse, these intrinsic optical signals are intimately related to the arrival of the action potential E-wave and the release of arginine vasopressin and oxytocin (S-wave). Here we have used a high bandwidth atomic force microscope to demonstrate that these light-scattering signals are associated with changes in terminal volume that are detected as nanometer-scale movements of a cantilever positioned on top of the neurohypophysis. The most rapid mechanical response ("spike"), having a duration shorter than the action potential but comparable to that of the E-wave, represents a transient increase in terminal volume due to water movement associated with Na(+)-influx. The slower mechanical event ("dip"), on the other hand, depends upon Ca(2+)-entry as well as on intraterminal Ca(2+)-transients and, analogously to the S-wave, seems to monitor events associated with secretion.

Optical methods are shown to monitor action potentials from a population of nerve terminals in the neurohypophysis of Xenopus. Calcium antagonists such as cadmium and nickel ions block a component of the action potential that probably reflects a calcium-mediated potassium conductance, and tetrodotoxin blocks an inward sodium current, revealing a calcium component to the action potential upstroke.

Large changes in the opacity of the unstained mouse neurohypophysis follow membrane potential changes known to trigger the release of peptide hormones . These intrinsic optical signals, arising in neurosecretory terminals, reflect variations in light scattering and depend upon both the frequency of stimulation and [Ca 21J. . Their magnitude is decreased in the presence of Ca2' antagonists and by the replacement of H2O in the medium by D20 . These observations suggest a correspondence between the intrinsic optical changes and secretory activity in these nerve terminals.