Large neurohypophysial varicosities amplify action potentials: results from numerical simulations.

Axons in the neurohypophysis are known for their "beads on a string" morphology, with numerous in-line secretory swellings lined up along the axon cable. A significant fraction of these secretory swellings, called Herring bodies, is large enough to serve as an identifying feature of the neural lobe in histological sections. Little is known about the physiological role such large axonal swellings might play in neuroendocrine physiology. Using numerical simulations, we have investigated whether large in-line varicosities affect the waveform and propagation of action potentials (APs) along neurohypophysial axons. Due to the strong nonlinear dependence of calcium influx on AP waveforms, such modulation would inevitably affect neuroendocrine release. The parameters for our numerical simulations were matched to established properties of voltage-gated ion channels in neurohypophysial swellings. We find that even a single in-line varicosity can severely depress AP waveforms far upstream in the axonal cable. In contrast, AP depolarization within varicosities becomes amplified. Amplification within varicosities varies in a nontrivial manner with varicosity dimensions, and is most pronounced for diameters close to those of Herring bodies. Overall, we find that large axonal varicosities significantly modulate AP waveforms and their propagation, and do so over large distances. Varicosity size is the main determinant for the observed AP amplification, with the kinetics of voltage-gated ion channels playing a noticeable but secondary role. Our results imply that large varicosities are sites of enhanced hormone release, suggesting that small and large varicosities target different neurohypophysial structures.