title: Inhibition of human acid-sensing ion channel 1b by zinc.
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 Ca(2+), 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.
authors: Qian
authors: Q
authors: Jiang
authors: Xiang-Ming
authors: XM
authors: Zha
authors: Xiang-Ping
authors: XP
authors: Chu