Acid-Sensing Ion Channel Pharmacology, Past, Present, and Future …

Advances in Pharmacology
Lachlan D Rash

Abstract

pH is one of the most strictly controlled parameters in mammalian physiology. An extracellular pH of ~7.4 is crucial for normal physiological processes, and perturbations to this have profound effects on cell function. Acidic microenvironments occur in many physiological and pathological conditions, including inflammation, bone remodeling, ischemia, trauma, and intense synaptic activity. Cells exposed to these conditions respond in different ways, from tumor cells that thrive to neurons that are either suppressed or hyperactivated, often fatally. Acid-sensing ion channels (ASICs) are primary pH sensors in mammals and are expressed widely in neuronal and nonneuronal cells. There are six main subtypes of ASICs in rodents that can form homo- or heteromeric channels resulting in many potential combinations. ASICs are present and activated under all of the conditions mentioned earlier, suggesting that they play an important role in how cells respond to acidosis. Compared to many other ion channel families, ASICs were relatively recently discovered-1997-and there is a substantial lack of potent, subtype-selective ligands that can be used to elucidate their structural and functional properties. In this chapter I cover the history of A...Continue Reading

Citations

Jul 24, 2018·Immunopharmacology and Immunotoxicology·Gui-Mei YuBao-Hua Liu
Oct 14, 2017·Molecular Pharmacology·Axel SchmidtStefan Gründer
Jun 11, 2019·Synapse·Osvaldo D UchitelCarina Weissmann
Aug 23, 2019·Scientific Reports·Wei-Hsiang HsuYun-Lian Lin
Sep 24, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Luke A PattisonEwan St John Smith
May 30, 2019·International Journal of Molecular Sciences·Isabella SalzerStefan Boehm
Jul 26, 2018·Proceedings of the National Academy of Sciences of the United States of America·Min QiangRichard A Lerner
Mar 23, 2018·ACS Chemical Neuroscience·Omar AlijevicStephan Kellenberger
Nov 27, 2018·ACS Chemical Neuroscience·Maxim V NikolaevDenis B Tikhonov

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