The tarantula toxin psalmotoxin 1 inhibits acid-sensing ion channel (ASIC) 1a by increasing its apparent H+ affinity.
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.
Chen
Xuanmao
X
Department of Physiology ll, University of Tübingen, 72076 Tübingen, Germany.
Kalbacher
Hubert
H
Gründer
Stefan
S
D062565:Acid Sensing Ion Channels; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D010455:Peptides; D011485:Protein Binding; D011522:Protons; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism*; D013111:Spider Venoms / Q000008:administration & dosage*; D014982:Xenopus laevis
D062565:Acid Sensing Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C413209:PcTX1 protein, Psalmopoeus cambridgei; D010455:Peptides; D011522:Protons; D015222:Sodium Channels; D013111:Spider Venoms; D002118:Calcium