Acid sensing ion channels: coincident detection of ischemia by a channel-channel interaction

Acid‑sensing ion channels are sodium‑selective channels gated by extracellular protons and are known to play a role in sensing ischemic conditions. Ischemia occurs when a tissue receives insufficient oxygen to meet its metabolic demands, leading to metabolic imbalance, pain, and tissue damage. A longstanding paradox has been how acid‑sensing ion channels function effectively within the complex ischemic environment. The work presented in this dissertation addresses this question and describes the discovery of a synergistic interaction between extracellular acidity and adenosine triphosphate (ATP) in modulating ion channel activity.