HYPOXIA-INDUCED DIFFERENTIAL ELECTROPHYSIOLOGICAL CHANGES IN RAT LOCUS-COERULEUS NEURONS

The effects of hypoxia on rat locus coeruleus (LC) neurons were invest igated by intracellular recording from in vitro brain slices. In respo nse to a brief exposure to hypoxic medium (2 - 5 min), equilibrated wi th 95 % N-2 - 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 neur ons ( 39 %), displaying gradual pure depolarization (6.0 +/- 0.3 mV, n = 80), instead of hypoxic hyperpolarization. Both types of response w ere 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 prope rties, their membrane input resistance differ significantly (type 1 ce lls: 144 +/- 5 M Ohm, n = 125; type 2 cells: 183 +/- 9 M Ohm, n = 80, p < 0.001). These responses were compared to cyanide-induced chemical hypoxia. Cyanide (2 mM) induced the identical membrane response as eff ected by nitrogen hypoxia. All cells which responded to nitrogen-satur ated hypoxic medium with a pure depolarizing response gave a similar r esponse 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 N-2-hypo xia-induced hyperpolarization was completely blocked by tolbutamide (2 00 mu M, n = 8) or glibenclamide (3 mu M, n = 9). These results indica te that a brief period of hypoxia evokes two different responses in LC neurons and this may be due to the heterogeneous distribution of K-AT P channels among different LC neurons.