Chapter 21 - Ion channels and the aging brain

Abstract

Ion channels comprise a large family of integral membrane proteins that operate in any organism, from bacteria to mammals, and are present in virtually any cell. Without channels, life, as we know would not be possible, and it is not coincidental that channels are implicated in aging as well. Here, we review the role of calcium (Ca2+) and potassium (K+) channels in the mechanisms underlying cognitive decline. As a result of modifications primarily due to oxidation of thiol groups by the reactive oxygen species that are liberated in the cells during aging, channels dysregulate calcium and potassium homeostases. Altered levels of calcium affect fundamental cellular properties such as phosphorylation and impact excitability both directly and indirectly by shifting the threshold for activation of calcium-activated K+ (K(Ca)) channels. Furthermore, oxidation of voltage-gated K+ channels dysregulate K+ homeostasis leading to hyperexcitability, inflammation, and neuronal loss. All together, these effects contribute to the cognitive decline of the normally aging and diseased brain. Therapeutic avenues that could treat neurological disease related to ion channel dysfunction are reviewed.