IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2011;3(4):288-309.

Review Article
Modulation of acid-sensing ion channels: molecular mechanisms and therapeutic

Xiang-Ping Chu, Christopher J. Papasian, John Q. Wang, Zhi-Gang Xiong

Department of Basic Medical Science, University of Missouri-Kansas City, Kansas City, MO 64108, USA; Department of Neurobiology,
Morehouse School of Medicine, Atlanta, GA30310, USA.

Received November 12, 2011; accepted November 17, 2011; Epub November 18, 2011; Published December 15, 2011

Abstract: Increases in extracellular proton concentrations, which takes place in physiological conditions such as synaptic signaling
and pathological conditions such as tissue inflammation, ischemic stroke, traumatic brain injury, and epileptic seizure, activates a
unique family of membrane ion channels; the acid-sensing ion channels (ASICs).  All ASICs belong to amiloride-sensitive
degenerin/epithelial Na+ channel superfamily. Four genes encoded at seven subunits have been identified. ASICs are expressed
primarily in neurons and have been shown to play critical roles in synaptic plasticity, learning/memory, fear conditioning, sensory
transduction, pain perception, ischemic brain injury, seizure, and other neurological as well as psychological disorders. Although
protons are the primary activator for ASICs, the properties and/or level of expression of these channels are modulated dramatically by
neuropeptides, di- and polyvalent cations, inflammatory mediators, associated proteins, and protein phosphorylations, etc. Modulation
of ASICs can result in profound changes in the activities and functions of these channels in both physiological and pathological
processes.  In this article, we provide an up to date review on the modulations of ASICs by exogenous agents and endogenous
signaling molecules. A better understanding of how ASICs can be modulated should help define new strategies to counteract the
deleterious effects of dysregulated ASIC activity.  (IJPPP1111001).

Keywords: Acid-sensing ion channel, acidosis, neuron, modulation

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Address all correspondence to:
Dr. Xiang-Ping Chu
Department of Basic Medical Science
School of Medicine
University of Missouri-Kansas City
2411 Holmes Street, Kansas City, MO 64108, USA.
Tel. (816) 235-2248
Fax. (816) 235-6517
E-mail: chux@umkc.edu

Dr. Zhi-Gang Xiong
Department of Neurobiology
Morehouse School of Medicine
720 Westview Drive SW
Atlanta, GA 30310, USA.
Tel. (404) 752-8683
Fax. (404) 752-1041
E-mail: zxiong@msm.edu