Insights into the molecular determinants of proton inhibition in an acid-inactivated degenerins and mammalian epithelial Na(+) channel.

ABSTRACT: Mammalian ASIC channels of the DEG/ENaC superfamily are gated by extracellular protons and function to mediate touch and pain sensitivity, learning and memory, and fear conditioning. The recently solved crystal structure of chicken ASIC1a and preliminary functional studies suggested that a highly negatively charged pocket in the extracellular domain of the channel might be the primary proton binding domain. However, more recent extensive mutagenesis analysis paints a more complex mechanism of channel gating, involving binding of protons at sites immediately after the first transmembrane domain (TM1) and displacement of inhibitory Ca(2+) ions from the acidic pocket in the extracellular domain and from another Ca(2+) binding site at the mouth of the pore. We recently identified and functiona

SUBMITTER: Wang Y 

PROVIDER: S-EPMC2764801 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature