Abstract
Acid-sensing ion channels (ASICs) are ion channels activated by extracellular protons. They are involved in higher brain functions and perception of pain, taste, and mechanical stimuli. Homomeric ASIC1a is potently inhibited by the tarantula toxin psalmotoxin 1. The mechanism of this inhibition is unknown. Here we show that psalmotoxin 1 inhibits ASIC1a by a unique mechanism: the toxin increases the apparent affinity for H+ of ASIC1a. Since ASIC1a is activated by H+ concentrations that are only slightly larger than the resting H+ concentration, this increase in H+ affinity is sufficient to shift ASIC1a channels into the desensitized state. As activation of ASIC1a has recently been linked to neurodegeneration associated with stroke, our results suggest chronic desensitization of ASIC1a by a slight increase of its H+ affinity as a possible way of therapeutic intervention in stroke.
Department
Molecular, Cellular and Biomedical Sciences
Publication Date
6-13-2005
Journal Title
Journal of General Physiology (JGP)
Publisher
Rockefeller University Press
Digital Object Identifier (DOI)
Document Type
Article
Recommended Citation
Chen X, Kalbacher H, Grunder S. The tarantula toxin psalmotoxin 1 inhibits acid-sensing ion channel (ASIC) 1a by increasing its apparent H+ affinity. The Journal of general physiology. 2005;126(1):71-9. doi: 10.1085/jgp.200509303. PubMed PMID: 15955877; PubMed Central PMCID: PMC2266618.
Comments
©Chen X, Kalbacher H, Grunder S, 2005. Originally published in Journal of General Physiology's (JGP). https://dx.doi.org/10.1085/jgp.200509303