Neuroprotective role of ATP-sensitive potassium channels in cerebral ischemia

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.

Mitochondrial Reactive Oxygen Species and Vascular Function

“…This study supports the role of mitochondrial ROS as signaling molecules that regulate endothelial cell function, and ultimately cerebral vascular tone. Although the connection involving the mito K ATP channel and mitochondrial-derived ROS has proven to be key in limiting ischemia/reperfusion damage in myocardium, the current study supports prior work 28 that sets the stage to explore these beneficial mechanisms in the cerebral vasculature as well, contributing to the concept of targeting mitochondria as a novel therapeutic target in the treatment of stroke.…”

Naringin protects cardiomyocytes against hyperglycemia-induced injuries in vitro and in vivo

“…An increase in the ATP/ADP ratio closes K ATP channels (which leads to depolarization), whereas a decrease in the ATP/ADP ratio opens K ATP channels (which leads to hyperpolarization) (Sun & Feng 2013). These changes suggest that HG both opened and inhibited the expression level of K ATP channels.…”

The Delta-Opioid Receptor Agonist D-Ala2-D-Leu2-Enkephalin Enhances Hypoxic Depression of Excitatory Synaptic Transmission and Improves Recovery of Rat Cortical Neurons from Hypoxia in vitro

“…This hypoxia-induced outward current through K ATP channels presumably protects type B neurons, by leading to hyperpolarisation of neurons and reducing the activity of ion pumps that consume a great amount of energy [25,42] . Accordingly, experimental evidence suggests that overexpression of subunits of these K ATP channels decreases ischemic cellular damage [26] .…”

“…Naloxone was chosen because DADLE is also known to activate mu-receptors at micromolar concentrations [26] , even though the expression of DOR in the cortex is higher compared to mu-opioid and kappa-opioid receptors [36] .…”