Effects of anoxia on rat midbrain dopamine neurons.
1. Dopamine-containing neurons of the rat midbrain were recorded intracellularly in vitro. Anoxia (2-5 min) caused reversible membrane hyperpolarization (4-25 mV), which blocked spontaneous firing of action potentials. Under voltage clamp, anoxia produced an outward current (100-1,000 pA) associated with an increase in the apparent input conductance. 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 control) reduced the anoxia-induced outward current. 4. Extracellular barium (0.1-1 mM) blocked the anoxia-induced hyperpolarization/outward current. Other K+ channel blockers (tetraethylammonium, apamin, quinine, and glibenclamide) failed to reduce anoxia-induced current. 5. When the dopamine-containing neurons were loaded with cesium (1-2 mM), anoxia caused a reversible membrane depolarization and a block of the firing activity. This depolarization was voltage dependent; it was decreased or blocked by the hyperpolarization of the membrane. 6. Perfusion of the cells with 0.5-1 microM TTX did not affect the membrane depolarization/inward current caused by anoxia. These were also present when the cells were treated with the excitatory amino acid receptor antagonists D,L-2-amino-5-phosphonovalerate (APV) (30 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 microM). 7. The exposure of the neurons with low-sodium, low-calcium solutions reversibly reduced the depolarizing/inward effects of anoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Mercuri
N B
NB
Clinica Neurologica, Università di Tor Vergata, Roma, Italy.
Bonci
A
A
Johnson
S W
SW
Stratta
F
F
Calabresi
P
P
Bernardi
G
G
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D046508:Culture Techniques; D004298:Dopamine / Q000502:physiology*; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008636:Mesencephalon / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology*
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D004298:Dopamine