An osmosensitive voltage-gated K+ current in rat supraoptic neurons

Eur J Neurosci. 2009 Jun;29(12):2335-46. doi: 10.1111/j.1460-9568.2009.06772.x. Epub 2009 May 22.


The magnocellular neurosecretory cells of the hypothalamus (MNCs) regulate their electrical behaviour as a function of external osmolality through changes in the activity of osmosensitive ion channels. We now present evidence that the MNCs express an osmosensitive voltage-gated K(+) current (the OKC). Whole-cell patch-clamp experiments on acutely isolated MNCs were used to show that increases in the external osmolality from 295 to 325 mosmol/kg cause an increase in a slow, tetraethylammonium-insensitive outward current. The equilibrium potential for this current is close to the predicted E(K) in two different concentrations of external K(+). The OKC is sensitive to block by Ba(2+) (0.3 mm), and by the M-type K(+) current blockers linopirdine (150 microm) and XE991 (5 microm), and to enhancement by retigabine (10 microm), which increases opening of M-type K(+) channels. The OKC is suppressed by muscarine (30 microm) and is decreased by the L-type Ca(2+) channel blocker nifedipine (10 microm), but not by apamin (100 nm), which blocks SK-type Ca(2+)-dependent K(+) currents. Reverse transcriptase-polymerase chain reaction and immunocytochemical data suggest that MNCs express several members of the K(V)7 (KCNQ) family of K(+) channels, including K(V)7.2, 7.3, 7.4 and 7.5. Extracellular recordings of individual MNCs in a hypothalamic explant preparation demonstrated that an XE991- and retigabine-sensitive current contribute to the regulation of MNC firing. Our data suggest that the MNCs express an osmosensitive K(+) current that could contribute to the regulation of MNC firing by external osmolality and that could be mediated by K(V)7/M-type K(+) channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / genetics
  • Animals
  • Anticonvulsants / pharmacology
  • Barium / pharmacology
  • Carbamates / pharmacology
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • KCNQ2 Potassium Channel / agonists
  • KCNQ2 Potassium Channel / antagonists & inhibitors
  • KCNQ2 Potassium Channel / metabolism
  • Male
  • Neurons / drug effects
  • Neurons / metabolism*
  • Organ Culture Techniques
  • Osmolar Concentration
  • Patch-Clamp Techniques
  • Phenylenediamines / pharmacology
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels, Voltage-Gated / agonists
  • Potassium Channels, Voltage-Gated / antagonists & inhibitors
  • Potassium Channels, Voltage-Gated / metabolism*
  • Rats
  • Rats, Long-Evans
  • Supraoptic Nucleus / drug effects
  • Supraoptic Nucleus / metabolism*
  • Water-Electrolyte Balance / drug effects
  • Water-Electrolyte Balance / physiology*


  • Anticonvulsants
  • Carbamates
  • KCNQ2 Potassium Channel
  • Phenylenediamines
  • Potassium Channel Blockers
  • Potassium Channels, Voltage-Gated
  • ezogabine
  • Barium