title: An osmosensitive voltage-gated K+ current in rat supraoptic neurons.
abstract: 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.
authors.affiliation: Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhang
authors.forename: Daoyi
authors.initials: D
authors.lastname: Wang
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Liu
authors.forename: W R A
authors.initials: WR
authors.lastname: Kosala
authors.forename: J S
authors.initials: JS
authors.lastname: Rajapaksha
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Fisher
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D051658:KCNQ2 Potassium Channel / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D010655:Phenylenediamines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*
chemical_list: D000927:Anticonvulsants; D002219:Carbamates; D051658:KCNQ2 Potassium Channel; D010655:Phenylenediamines; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; C101866:ezogabine; D001464:Barium