Protective role of neuronal KATP channels in brain hypoxia.
During severe arterial hypoxia leading to brain anoxia, most mammalian neurons undergo a massive depolarisation terminating in cell death. However, some neurons of the adult brain and most immature nervous structures tolerate extended periods of hypoxia-anoxia. An understanding of the mechanisms underlying this tolerance to oxygen depletion is pivotal for developing strategies to protect the brain from consequences of hypoxic-ischemic insults. ATP-sensitive K(+) (K(ATP)) channels are good subjects for this study as they are activated by processes associated with energy deprivation and can counteract the terminal anoxic-ischemic neuronal depolarisation. This review summarises in vitro analyses on the role of K(ATP) channels in hypoxia-anoxia in three distinct neuronal systems of rodents. In dorsal vagal neurons, blockade of K(ATP) channels with sulfonylureas abolishes the hypoxic-anoxic hyperpolarisation. However, this does not affect the extreme tolerance of these neurons to oxygen depletion as evidenced by a moderate and sustained increase of intracellular Ca(2+) (Ca(i)). By contrast, a sulfonylurea-induced block of K(ATP) channels shortens the delay of occurrence of a major Ca(i) rise in cerebellar Purkinje neurons. In neurons of the neonatal medullary respiratory network, K(ATP) channel blockers reverse the anoxic hyperpolarisation associated with slowing of respiratory frequency. This may constitute an adaptive mechanism for energy preservation. These studies demonstrate that K(ATP) channels are an ubiquituous feature of mammalian neurons and may, indeed, play a protective role in brain hypoxia.
Ballanyi
Klaus
K
Department of Physiology & Pediatrics, Perinatal Research Centre, University of Alberta, 232 HMRC, Edmonton, Alberta, T6G 2S2, Canada. klaus.ballanyi@ualberta.ca
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D002534:Hypoxia, Brain / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D012119:Respiration; D013453:Sulfonylurea Compounds / Q000378:metabolism
D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D000255:Adenosine Triphosphate; D010100:Oxygen; D002118:Calcium