title: Hypoxia-induced differential electrophysiological changes in rat locus coeruleus neurons.
abstract: The effects of hypoxia on rat locus coeruleus (LC) neurons were investigated by intracellular recording from in vitro brain slices. In response to a brief exposure to hypoxic medium (2-5 min), equilibrated with 95% N2 - 5% CO2, two populations of cells could be distinguished, type 1 neurons (61%), showing hyperpolarization (9.3 +/- 0.4 mV, n = 125) and cessation of spontaneous action potentials, and type 2 neurons (39%), displaying gradual pure depolarization (6.0 +/- 0.3 mV, n = 80), instead of hypoxic hyperpolarization. Both types of response were associated with a reduction in membrane input resistance (34 +/- 1% for type 1 cells, n = 125, and 21 +/- 2% for type 2 cells, n = 68). While both types of neurons share similar electrophysiological properties, their membrane input resistance differ significantly (type 1 cells: 144 +/- 5 M omega, n = 125; type 2 cells: 183 +/- 9 M omega, n = 80, p < 0.001). These responses were compared to cyanide-induced chemical hypoxia. Cyanide (2 mM) induced the identical membrane response as effected by nitrogen hypoxia. All cells which responded to nitrogen-saturated hypoxic medium with a pure depolarizing response gave a similar response to cyanide and all neurons hyperpolarized by cyanide were also hyperpolarized by hypoxic medium. Moreover, the K(ATP) channel opener, diazoxide (1 mM), could mimic the hypoxia-induced hyperpolarization in type 1 neurons (10.6 +/- 0.9 mV, n = 18), but was unable to induce hyperpolarization in type 2 cells (n = 13). In addition, the N2-hypoxia-induced hyperpolarization was completely blocked by tolbutamide (200 microM, n = 8) or glibenclamide (3 microM, n = 9). These results indicate that a brief period of hypoxia evokes two different responses in LC neurons and this may be due to the heterogeneous distribution of K(ATP) channels among different LC neurons.
authors.affiliation: Department of Physiology, National Yang Ming University, Taipei, Taiwan, Republic of China.
authors.forename: J J
authors.initials: JJ
authors.lastname: Yang
authors.forename: Y C
authors.initials: YC
authors.lastname: Chou
authors.forename: M T
authors.initials: MT
authors.lastname: Lin
authors.forename: T H
authors.initials: TH
authors.lastname: Chiu
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D003486:Cyanides / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003486:Cyanides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D003981:Diazoxide