IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2012;4(2):84-93.

Original Article
Inhibition of human acid-sensing ion channel 1b by zinc

Qian Jiang, Xiang-Ming Zha, Xiang-Ping Chu

Department of Basic Medical Science, University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USA;
Department of Cell Biology and Neuroscience, University of South Alabama College of Medicine, Mobile, AL 36688, USA

Received April 4, 2012; accepted May 8, 2012; Epub June 20, 2012; Published June 30, 2012

Abstract: Acid-sensing ion channel 1b (ASIC1b) is expressed in peripheral sensory neurons and has been implicated in nociception.
Understanding the modulation of ASIC1b will provide important insight into how ASIC1b contributes to pain sensation. In our previous
study, we showed that zinc, an important modulator of pain sensation, reduces rat ASIC1b current. However, rat ASIC1b shows several
important differences from its recently identified human homolog. Most noticeably, human ASIC1b (hASIC1b) has a sustained
component, which may play a role in persistent pain. Therefore, we tested here the hypothesis that zinc modulates the current
properties of hASIC1b. Bath application of zinc suppressed the peak amplitude of hASIC1b currents, with a half-maximum inhibitory
concentration of 37 µM. However, zinc did not affect the sustained component of hASIC1b currents. The effect of zinc was independent
of pH-dependent activation, steady-state desensitization, and extracellular Ca2+, suggesting noncompetitive mechanisms. Further, we
found that extracellular site(s) of the hASIC1b subunit is important for the effect of zinc. Mutating cysteine 196, but not cysteine 309, in
the extracellular domain of the hASIC1b abolished the zinc inhibition. These results suggest that, through modulating cysteine196, zinc
may have a modulatory role in acute pain. (IJPPP1204001)

Keywords: Acid-sensing ion channels, zinc, hASIC1b, patch-clamp, pain

Address all correspondence to:
Dr. Xiang-Ping Chu
Department of Basic Medical Science
University of Missouri-Kansas City School of Medicine
2411 Holmes Street, Kansas City, MO 64108, USA.
Tel: +1-816-235-2248; Fax: +1-816-235-6517
E-mail: chux@umkc.edu