EFFECTS OF ANOXIA ON RAT MIDBRAIN DOPAMINE NEURONS

1. Dopamine-containing neurons of the rat midbrain were recorded intra cellularly in vitro. Anoxia (2-5 min) caused reversible membrane hyper polarization (4-25 mV), which blocked spontaneous firing of action pot entials. Under voltage clamp, anoxia produced an outward current (100- 1,000 pA) associated with an increase in the apparent input conductanc e. 2. The mean reversal potential of the anoxia-induced response at 2. 5 and 12.5 mM [K+] was -86 and -66 mV, respectively. 3. The effect of anoxia was not blocked by tetrodotoxin (TTX), saclofen, (-)sulpiride, or strychnine. Superfusate containing low calcium (0.5 mM CaCl2 and 10 mM MgCl2 or 0.5-1 mM CaCl2 and 1 mM CoCl2) or low sodium (25-40% of c ontrol) reduced the anoxia-induced outward current. 4. Extracellular b arium (0.1-1 mM) blocked the anoxia-induced hyperpolarization/outward current. Other K+ channel blockers (tetraethylammonium, apamin, quinin e, and glibenclamide) failed to reduce anoxia-induced current. 5. When the dopamine-containing neurons were loaded with cesium (1-2 mM), ano xia caused a reversible membrane depolarization and a block of the fir ing activity. This depolarization was voltage dependent; it was decrea sed or blocked by the hyperpolarization of the membrane. 6. Perfusion of the cells with 0.5-1 mu M TTX did not affect the membrane depolariz ation/inward current caused by anoxia. These were also present when th e cells were treated with the excitatory amino acid receptor antagonis ts D,L-2-amino-5-phosphono-valerate (APV) (30 mu M) and 6-cyano-7-nitr oquinoxaline-2,3-dione (CNQX) (10 mu M). 7. The exposure of the neuron s with low-sodium, low-calcium solutions reversibly reduced the depola rizing/inward effects of anoxia. 8. It is concluded that under control condition anoxia hyperpolarizes dopamine-containing neurons. However, when the potassium current is blocked by intracellular cesium, it dep olarizes these cells.