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Acid-sensing ion channels and their modulators

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Abstract

According to a modern look acid-sensing ion channels (ASICs) are one of the most important receptors that perceive pH change in the body. ASICs represent proton-gated Na+-selective channels, which are expressed in neurons of the central and peripheral nervous system. These channels are attracting attention of researchers around the world, as they are involved in various physiological processes in the body. Drop of pH may occur in tissues in norm (e.g. the accumulation of lactic acid, the release of protons upon ATP hydrolysis) and pathology (inflammation, ischemic stroke, tissue damage and seizure). These processes are accompanied by unpleasant pain sensations, which may be short-lived or can lead to chronic inflammatory diseases. Modulators of ASIC channels activity are potential candidates for new effective analgesic and neuroprotection drugs. This review summarizes available information about structure, function, and physiological role of ASIC channels. In addition a description of all known ligands of these channels and their practical relevance is provided.

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Abbreviations

AA:

arachidonic acid

ASIC:

acid-sensing ion channel

CNS:

central nervous system

DEG/ENaC:

amiloride-sensitive degenerin/epithelial Na+ channel

EPSP:

excitable postsynaptic potential

GMQ:

2-guanidine-4-methylquinazolin

NSAIDs:

nonsteroidal antiinflammatory drugs

PcTx1:

psalmotoxin 1

SLP3:

stomatin-like protein 3

TM:

transmembrane domain

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  1. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia

    D. I. Osmakov, Ya. A. Andreev & S. A. Kozlov

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Original Russian Text © D. I. Osmakov, Ya. A. Andreev, S. A. Kozlov, 2014, published in Uspekhi Biologicheskoi Khimii, 2014, Vol. 54, pp. 231–266.

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Osmakov, D.I., Andreev, Y.A. & Kozlov, S.A. Acid-sensing ion channels and their modulators. Biochemistry Moscow 79, 1528–1545 (2014). https://doi.org/10.1134/S0006297914130069

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