Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels

Acid sensing is associated with nociception, taste transduction, and percep tion 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 a cid-sensitive ion channel (ASIC) family. Toxins from animal venoms have bee n essential for studies of voltage-sensitive and ligand-gated ion channels. This paper describes a novel 40-amino acid toxin from tarantula venom, whi ch potently blocks (IC50 = 0.9 nM) a particular subclass of ASIC channels t hat are highly expressed in both central nervous system neurons and sensory neurons from dorsal root ganglia. This channel type has properties identic al to those described for the homomultimeric assembly of ASIC1a. Homomultim eric assemblies of other members of the ASIC family and heteromultimeric as semblies of ASIC1a with other ASIC subunits are insensitive to the toxin. T he new toxin is the first high affinity and highly selective pharmacologica l agent for this novel class of ionic channels. It will be important for fu ture studies of their physiological and physio-pathological roles.