Mechanisms of neuronal survival during hypoxia: ATP-sensitive K+ channels.

There has been an explosion in our understanding of how nerve cells in mammals respond to O2 deprivation and what are the mechanisms involved in nerve cell injury or survival. This is due to the development of new approaches, techniques and the clinical importance of brain ischemia and hypoxia. Recently, we have focussed on some issues pertaining to brain hypoxia in the newborn and adult. We have demonstrated that during anoxia intracellular K+ decreases significantly in nerve cells and that this K+ efflux is mediated by K+ channels that are sensitive to ATP. We have preliminary evidence that the activation of these channels attenuates the anoxia-induced depolarization in medullary neurons and can play a role in cell survival during anoxia. Further, we have characterized the distribution of these receptors/channels complexes in the CNS of the rat and in an anoxia-resistant animal: the turtle. These channels are present mainly in the cortex, substantia nigra and the cerebellum. Whole cell recordings (dissociated cells) established that these channels are postsynaptic in nature in medullary neurons. Single-channel recordings from our laboratory and those of others have started to reveal the intricacies of the regulation of these channels in excitable cells in general and in nerve cells in particular.