Osmotic activation of phospholipase C triggers structural adaptation in osmosensitive rat supraoptic neurons

J Physiol. 2014 Oct 1;592(19):4165-75. doi: 10.1113/jphysiol.2014.273813. Epub 2014 Jul 11.


The magnocellular neurosecretory cells of the hypothalamus (MNCs) synthesize and secrete vasopressin or oxytocin. A stretch-inactivated cation current mediated by TRPV1 channels rapidly transduces increases in external osmolality into a depolarization of the MNCs leading to an increase in action potential firing and thus hormone release. Prolonged increases in external osmolality, however, trigger a reversible structural and functional adaptation that may enable the MNCs to sustain high levels of hormone release. One poorly understood aspect of this adaptation is somatic hypertrophy. We demonstrate that hypertrophy can be evoked in acutely isolated rat MNCs by exposure to hypertonic solutions lasting tens of minutes. Osmotically evoked hypertrophy requires activation of the stretch-inactivated cation channel, action potential firing, and the influx of Ca(2+). Hypertrophy is prevented by pretreatment with a cell-permeant inhibitor of exocytotic fusion and is associated with an increase in total membrane capacitance. Recovery is disrupted by an inhibitor of dynamin function, suggesting that it requires endocytosis. We also demonstrate that hypertonic solutions cause a decrease in phosphatidylinositol 4,5-bisphosphate in the plasma membranes of MNCs that is prevented by an inhibitor of phospholipase C (PLC). Inhibitors of PLC or protein kinase C (PKC) prevent osmotically evoked hypertrophy, and treatment with a PKC-activating phorbol ester can elicit hypertrophy in the absence of changes in osmolality. These studies suggest that increases in osmolality cause fusion of internal membranes with the plasma membrane of the MNCs and that this process is mediated by activity-dependent activation of PLC and PKC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Cell Enlargement / drug effects*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Neurons / drug effects*
  • Neurons / physiology
  • Osmolar Concentration
  • Oxytocin / metabolism
  • Rats
  • Saline Solution, Hypertonic / pharmacology*
  • Supraoptic Nucleus / drug effects*
  • Supraoptic Nucleus / physiology
  • Type C Phospholipases / metabolism*
  • Vasopressins / metabolism


  • Saline Solution, Hypertonic
  • Vasopressins
  • Oxytocin
  • Type C Phospholipases