Cellular mechanisms of long‐term osmoregulation in magnocellular neurons

Osmoregulation is an essential homeostatic process that maintains the osmolality of the extracellular fluid (ECF) close to a physiological setpoint. Vasopressin (VP) plays a key role in osmoregulation and is secreted by the magnocellular neurosecretory cells (MNCs) of the hypothalamus. MNC electrical activity and VP release increase with elevations of ECF osmolality. MNC osmosensitivity depends on a mechanosensitive N‐terminal variant of the transient receptor potential vanilloid type 1 (ΔN‐TRPV1) channel that activates in response to osmotically induced cell shrinkage. ΔN‐TRPV1 mechanosensitivity depends on their association with microtubules in the MNC cytoskeleton and is modulated by a dense layer of submembranous actin in MNC somata. MNCs exposed to sustained increases in osmolality, however, undergo marked somatic hypertrophy, which suggests that other mechanisms may be important to maintain VP release. Recent evidence suggests that the translocation of ΔN‐TRPV1 (and possibly other channels) to the MNC cell surface could contribute to osmotically induced long‐term increases in MNC excitability. Osmotically induced ion channel translocation is dependent on MNC firing, Ca2+ influx through L‐type Ca2+ channels, the activation of phospholipase C δ1 and protein kinase C, and soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor‐dependent exocytotic fusion. Other recent work has explored osmotically induced changes in the MNC cytoskeleton that may be related to hypertrophy and ion channel translocation. MNCs may also be activated by elevations in extracellular Na+ through the activation of the Na+‐sensitive Na+ channel, NaX. This review highlights recent advancements in our understanding of long‐term MNC regulation at the cellular level.

• Publication year

  2025

• Venue

  Journal of neuroendocrinology

• Publication date

  2025-09-11

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1111/jne.70090PMID 40936216PMCID 12678019
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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