Responses of rat mesencephalic dopaminergic neurons to a prolonged period of oxygen deprivation

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

Research output: Contribution to journalArticlepeer-review

Abstract

We employed intracellular electrophysiological techniques to examine the effects of a prolonged anoxia (more than 7 min superfusion with artificial cerebrospinal fluid saturated with 95% N2-5% O2) on dopaminergic neurons of the rat ventral mesencephalon maintained in vitro. A prolonged anoxia caused an inhibition of the spontaneous firing and a sustained (mean 16 min) and slowly declining hyperpolarization of the membrane in 30 dopaminergic cells. This was associated with a decrease of the apparent input resistance at 5, 10, 15 and 20 min of O2 deprivation by 38% (n = 18), 42% (n = 18), 48% (n = 18) and 54% (n = 8) of control, respectively. The continuation of anoxia, 1-4 min after the hyperpolarizing period, induced an irreversible depolarization (n = 8). More than 50% of the cells (17 of 30) fully recovered their electrophysiological properties after 15 min of O2 deprivation. Since the intracellular diffusion of cesium (a potassium channel blocker) was able to block the hyperpolarization and to reveal a depolarization caused by anoxia, we tested whether the blockade of the hyperpolarization modified the resistance of the cells to O2 deprivation. We observed that the cells loaded with cesium were depolarized and damaged in a period of O2 deprivation less than 10 min. The apparent input resistance of these neurons was irreversibly reduced by 36% of the control at 5 min of anoxia (n =6). Furthermore, in order to ascertain whether an impairment of the sodium/potassium pump due to energy failure is involved in the anoxia-induced depolarization, we blocked the Na+/K+ ATPase pump with the inhibitor ouabain. In the presence of ouabain (1-10 μ M), the depolarization/inward current induced by a short-term anoxia (2-5 min) in cesium-loaded cells was augmented (n = 8) or became irreversible (n = 5). Our results suggest that 1. (i) the dopaminergic neurons stay hyperpolarized during a prolonged period of O2 deprivation and later depolarize after a certain time during anoxia, 2. (ii) the inhibition of the Na+/K+ ATP-dependent pump enhances the anoxia-induced depolarization and 3. (iii) the hyperpolarization of the membrane that develops during anoxia may play an important role in prolonging neuronal survival.

Original languageEnglish
Pages (from-to)757-764
Number of pages8
JournalNeuroscience
Volume63
Issue number3
DOIs
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Neuroscience(all)

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