Targeting Acid-Sensing Ion Channels in Disease
摘要
Acidosis is a central feature of many pathological conditions, and while the activity of many ion channels is suppressed under acidic conditions, acid-sensing ion channels (ASICs) are exquisitely sensitive to decreases in pH and activated by protons. The expression and function of ASICs is enhanced under conditions of ischemia, inflammation, and trauma. Here, we will focus on this family of ion channels whose main role appears to be the detection of perturbations to local tissue pH, and review the evidence for their role, and whether they represent viable druggable targets in a multitude of currently poorly treated conditions. This chapter provides an overview of the key evidence for the role of ASICs in pathological states, a commentary on their potential as therapeutic targets in humans identifying several major challenges we face in developing ASIC targeting therapies.