IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2010;2(1):73-94.

Review Article
Structure, function, and pharmacology of acid-sensing ion channels (ASICs): focus
on ASIC1a.

Stefan Gründer, Xuanmao Chen

Department of Physiology, RWTH Aachen University, Aachen, Germany, Department of Physiology, University of Toronto, Toronto,

Received February 16, 2010, accepted March 10, 2010, available online March 18, 2010

Abstract: Acid-sensing ion channels (ASICs) are H+-gated Na+ channels, which are present in most, if not all, neurons. The typical
ASIC current is transient and is elicited by a rapid drop in the extracellular pH. In the human genome, four genes for ASICs are present:
asic1 – 4. In this review, we will focus on ASIC1a, one of the key subunits in the central nervous system. We will describe the structure
of this channel, a topic that has enormously profited from the recent elucidation of the first crystal structure of an ASIC. We will then
relate the ASIC1 structure to current models of the gating mechanism of ASICs. Finally, we will review the pharmacology of ASIC1a.
Advances in the pharmacological inhibition of individual ASIC currents have greatly contributed to our current knowledge of the
functional roles of this channel in physiology, including learning, memory, and fear conditioning, and in pathophysiological states,
including the neurodegeneration accompanying stroke, and axonal degeneration in autoimmune inflammation. (IJPPP1002001).

Key words: Acidosis, desensitization, excitatory postsynaptic current, fear conditioning, ischemia, psalmotoxin

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Address all correspondence to:
Stefan Gründer, PhD
Department of Physiology
RWTH Aachen University
Aachen, Germany

Xuanmao Chen, PhD
Department of Physiology
University of Toronto
Toronto, Canada