Dietary supplements influence activity of acid‐sensing ion channels (1061.8)

Dietary supplements and nutraceuticals have been the focus of research to identify novel therapeutics for a variety of pathologies, including the prevention of long‐term consequences of stroke and reducing pain. Ion channels offer a growing group of molecular targets for treatment, which include the acid‐sensing ion channels (ASICs). Acid‐sensing ion channels (ASICs) are sodium channels that are sensitive to changes in extracellular pH, specifically those changes following injury and ischemia. These channels are expressed most prominently in peripheral and central nervous system. Their role in physiology is yet to be fully understood, but these channels have been implicated in pain sensation and centrally in the neurodegeneration following ischemic stroke. We identified an over‐the‐counter dietary supplement (DS) that shares similarity to guanidine compounds that selectively modulate acid‐sensing ion channels. Thus, we hypothesize that this dietary supplement inhibits channel activity in acid‐sensing ion channels. Our preliminary data show that DS decreased the ASIC1a pH sensitivity by shifting the observed proton activation profile to the right. Furthermore, we observed a change in the Hill coefficient of the DS influenced ASIC1a steady‐state desensitization profile. Future experiments will focus on determining the influence of DS on other acid‐sensing ion channel subtypes and identifying the DS binding site with the protein structure. Grant Funding Source : American Heart Association 12BGIA8820001