Agharkar, Amruta S.
Gonzales, Eric B.


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Dietary supplements or nutraceutical industry contributes billions of dollars to Unites States economy every year. The dietary supplement we intend to study is one of the most commonly used nutraceutical available in the market over the counter. It is used primarily by athletes and body builders to build lean body mass. Studies have shown that DS is effective in neuroprotection after stroke and also helps in improving muscle strength in patients suffering from muscle weakness or osteoarthritis. We are studying the effect of DS on acid-sensing ion channels (ASICs) which are the major contributors to neuronal damage after ischemia and pain. Determining the activity of DS on ASICs will give the new preventive measure for stroke and pain. Purpose (a): 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. Methods (b): We will utilize whole cell patch-clamp electrophysiology technique to determine the intrinsic activity of DS on ASICs. The current elicited in absence and presence of DS at various pH will be normalized to maximum peak current obtained with control. Results (c): 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. Conclusions (d): Based on our preliminary data, we can conclude that DS influences ASIC current amplitude and 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.