The Effect of Hypoxia on Hippocampal Neurones and its Prevention by Ca2+-Antagonists

Abstract

The effects of hypoxia and high-potassium media on the rat hippocampal CA1 neurones in tissue slices were studied using intracellular electrodes. In response to superfusion with a hypoxic medium, a majority of the neurones showed a transient hyperpolarization followed by a slow depolarization at a plateau level of about 25 mV from the pre-hypoxic resting potential, and that evoked e.p.s.p.s were well preserved during hypoxic exposure. These results suggest that low oxygen tension per se may not be the major cause of neuronal dysfunction due to hypoxic hypoxia or ischaemia. In a minority of the neurones the slow depolarization was followed by a rapid depolarization, after which the neurones showed no functional recovery. Further analyses suggest that a marked influx of calcium ions probably triggers irreversible processes. In response to superfusion with potassium-rich (≥ 60 mM) media, all the neurones showed a marked depolarization of approximately 60 mV, and the membrane potential was irreversibly reduced to 0 mV even after washing out the media. The membrane dysfunction was blocked by removal of calcium or chloride ions, or addition of cobalt or organic calcium channel antagonists to the extracellular solution. In addition to these findings, the ionic mechanisms underlying the potential changes induced by hypoxia and the cause of the membrane dysfunction produced by potassium-rich media have been discussed.