Mechanical Basis of Osmosensory Transduction in Magnocellular Neurosecretory Neurones of the Rat Supraoptic Nucleus

Rat magnocellular neurosecretory cells ( MNC s) release vasopressin and oxytocin to promote antidiuresis and natriuresis at the kidney. The osmotic control of oxytocin and vasopressin release at the neurohypophysis is required for osmoregulation in these animals, and this release is mediated by a modulation of the action potential firing rate by the MNC s. Under basal (isotonic) conditions, MNC s fire action potentials at a slow rate, and this activity is inhibited by hypo‐osmotic conditions and enhanced by hypertonicity. The effects of changes in osmolality on MNC s are mediated by a number of different factors, including the involvement of synaptic inputs, the release of taurine by local glial cells and regulation of ion channels expressed within the neurosecretory neurones themselves. We review recent findings that have clarified our understanding of how osmotic stimuli modulate the activity of nonselective cation channels in MNC s. Previous studies have shown that osmotically‐evoked changes in membrane potential and action potential firing rate in acutely isolated MNC s are provoked mainly by a modulation of nonselective cation channels. Notably, the excitation of isolated MNC s during hypertonicity is mediated by the activation of a capsaicin‐insensitive cation channel that MNC s express as an N‐terminal variant of the transient receptor potential vanilloid 1 (Trpv1) channel. The activation of this channel during hypertonicity is a mechanical process associated with cell shrinking. The effectiveness of this mechanical process depends on the presence of a thin layer of actin filaments (F‐actin) beneath the plasma membrane, as well as a densely interweaved network of microtubules ( MT s) occupying the bulk of the cytoplasm of MNC s. Although the mechanism by which F‐actin contributes to Trpv1 activation remains unknown, recent data have shown that MT s interact with Trpv1 channels via binding sites on the C‐terminus, and that the force mediated through this complex is required for channel gating during osmosensory transduction. Indeed, displacement of this interaction prevents channel activation during shrinking, whereas increasing the density of these interaction sites potentiates shrinking‐induced activation of Trpv1. Therefore, the gain of the osmosensory transduction process can be regulated bi‐directionally through changes in the organisation of F‐actin and MT s.