A novel osmosensitive voltage gated cation current in rat supraoptic neurones

The magnocellular neurosecretory cells of the hypothalamus (MNCs) regulate water balance by releasing vasopressin and oxytocin as a function of plasma osmolality. Release is determined largely by the rate and pattern of action potentials generated in the MNC somata. Changes in firing are mediated in part by a stretch-inactivated non-selective cation current that causes the cells to depolarize when increased osmolality leads to cell shrinkage. We have obtained evidence for a new current that may regulate MNC firing during changes in external osmolality, using whole-cell patch clamp of acutely isolated rat MNC somata. In internal and external solutions lacking K+, with high concentrations of TEA, and with Na+ as the only likely permeant cation, the current appears as a slow inward current during depolarizations and yields a large tail current upon return to the holding potential of -80 mV. Approximately 60% of the MNCs tested (79 out of 134 cells) displayed a large increase in tail current density (from 5.2+/-0.9 to 10.5+/-1.4 pA pF-1; P<0.001) following an increase in external osmolality from 295 to 325 mosmol kg-1. The current is activated by depolarization to potentials above -60 mV and does not appear to depend on changes in internal Ca2+. The current is carried by Na+ under these conditions, but is blocked by Cs+ and Ba2+ and by internal K+, which suggests that the current could be a K+ current under physiological conditions. This current could play an important role in regulating the response of MNCs to osmolality.