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¹ Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5

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.

(Received 30 June 2005; accepted after revision 5 August 2005; first published online 11 August 2005)
Corresponding author T. E. Fisher: Department of Physiology, College of Medicine, 107 Wiggins Road, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5. Email: thomas.fisher{at}usask.ca

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