Abstract
ATP-sensitive potassium (K(ATP)) channels are weak, inward rectifiers that couple metabolic status to cell membrane electrical activity, thus modulating many cellular functions. An increase in the ADP/ATP ratio opens K(ATP) channels, leading to membrane hyperpolarization. K(ATP) channels are ubiquitously expressed in neurons located in different regions of the brain, including the hippocampus and cortex. Brief hypoxia triggers membrane hyperpolarization in these central neurons. In vivo animal studies confirmed that knocking out the Kir6.2 subunit of the K(ATP) channels increases ischemic infarction, and overexpression of the Kir6.2 subunit reduces neuronal injury from ischemic insults. These findings provide the basis for a practical strategy whereby activation of endogenous K(ATP) channels reduces cellular damage resulting from cerebral ischemic stroke. K(ATP) channel modulators may prove to be clinically useful as part of a combination therapy for stroke management in the future.