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ATP-sensitive potassium (K(ATP)) channels are weak inward rectifiers that appear to play an important role in protecting neurons against ischemic damage. Cerebral stroke is a major health issue, and vulnerability to stroke damage is regional within the brain. Thus, we set out to determine whether K(ATP) channels protect cortical neurons against ischemic insults. Experiments were performed using Kir6.2(-/-) K(ATP) channel knockout and Kir6.2(+/+) wildtype mice. We compared results obtained in Kir6.2(-/-) and wildtype mice to evaluate the protective role of K(ATP) channels against focal ischemia in vivo, and, using cortical slices, against anoxic stress in vitro. Immunohistochemistry confirmed the presence of K(ATP) channels in the cortex of wildtype, but not Kir6.2(-/-), mice. Results from in vivo and in vitro experimental models indicate that Kir6.2-containing K(ATP) channels in the cortex provide protection from neuronal death. Briefly, in vivo focal ischemia (15 min) induced severe neurological deficits and large cortical infarcts in Kir6.2(-/-) mice, but not in wildtype mice. Imaging analyses of cortical slices exposed briefly to oxygen and glucose deprivation (OGD) revealed a substantial number of damaged cells (propidium iodide-labeled) in the Kir6.2(-/-) OGD group, but few degenerating neurons in the wildtype OGD group, or in the wildtype and Kir6.2(-/-) control groups. Slices from the three control groups had far more surviving cells (anti-NeuN antibody-labeled) than slices from the Kir6.2(-/-) OGD group. These findings suggest that stimulation of endogenous cortical K(ATP) channels may provide a useful strategy for limiting the damage that results from cerebral ischemic stroke.

Original publication

DOI

10.1016/j.neuroscience.2006.10.043

Type

Journal article

Journal

Neuroscience

Publication Date

23/02/2007

Volume

144

Pages

1509 - 1515

Keywords

Animals, Brain Infarction, Cell Death, Cell Survival, Cerebral Cortex, Cytoprotection, Genetic Predisposition to Disease, Hypoxia-Ischemia, Brain, Male, Mice, Mice, Knockout, Nerve Degeneration, Neurons, Organ Culture Techniques, Potassium Channels, Inwardly Rectifying