Hypoxia-induced differential electrophysiological changes in rat locus coeruleus neurons

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.