Effects of anoxia on rat midbrain dopamine neurons

N. B. Mercuri, A. Bonci, S. W. Johnson, F. Stratta, P. Calabresi, G. Bernardi

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47 Scopus citations


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 μM 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 μM) and 6-cyano-7- nitroquinoxaline-2,3-dione (CNQX) (10 μM). 7. The exposure of the neurons with low-sodium, low-calcium solutions reversibly reduced the depolarizing/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 depolarizes these cells.

Original languageEnglish (US)
Pages (from-to)1165-1173
Number of pages9
JournalJournal of neurophysiology
Issue number3
StatePublished - 1994
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology


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