Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels.
Acid sensing is associated with nociception, taste transduction, and perception of extracellular pH fluctuations in the brain. Acid sensing is carried out by the simplest class of ligand-gated channels, the family of H(+)-gated Na(+) channels. These channels have recently been cloned and belong to the acid-sensitive ion channel (ASIC) family. Toxins from animal venoms have been essential for studies of voltage-sensitive and ligand-gated ion channels. This paper describes a novel 40-amino acid toxin from tarantula venom, which potently blocks (IC(50) = 0.9 nm) a particular subclass of ASIC channels that are highly expressed in both central nervous system neurons and sensory neurons from dorsal root ganglia. This channel type has properties identical to those described for the homomultimeric assembly of ASIC1a. Homomultimeric assemblies of other members of the ASIC family and heteromultimeric assemblies of ASIC1a with other ASIC subunits are insensitive to the toxin. The new toxin is the first high affinity and highly selective pharmacological agent for this novel class of ionic channels. It will be important for future studies of their physiological and physio-pathological roles.
Escoubas
P
P
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Sophia-Antipolis, Valbonne, France.
De Weille
J R
JR
Lecoq
A
A
Diochot
S
S
Waldmann
R
R
Champigny
G
G
Moinier
D
D
Ménez
A
A
Lazdunski
M
M
D062565:Acid Sensing Ion Channels; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D019556:COS Cells; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D015640:Ion Channel Gating; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry; D009474:Neurons / Q000187:drug effects; D009865:Oocytes / Q000378:metabolism; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry; D017510:Protein Folding; D011522:Protons; D051381:Rats; D017208:Rats, Wistar; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism*; D013111:Spider Venoms / Q000737:chemistry* / Q000302:isolation & purification*; D013112:Spiders / Q000737:chemistry; D014981:Xenopus
C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D018076:DNA, Complementary; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C413209:PcTX1 protein, Psalmopoeus cambridgei; D010455:Peptides; D011522:Protons; D015222:Sodium Channels; D013111:Spider Venoms