Cys-loop receptors (CLRs) are commonly known as ligand-gated channels (LGIC) that transiently open upon binding of neurotransmitters in order to modify the membrane potential. However, a class of cation selective bacterial homologues of CLRs have been found to open upon a sudden pH drop, suggesting further ligands and more functions of the homologues in prokaryotes. Here we report an anion selective CLR from the hydrothermal vent annelid worm Alvinella pompejana which opens at low pH. A. pompejana EST databases were explored by us and two full-length CLR sequences were identified, synthesized, cloned, expressed in Xenopus oocytes and studied by two electrode voltage clamp. One channel, named Alv-a1-pHCl, yielded functional receptors and opened upon a sudden pH drop but not by other known agonists. Sequence comparison showed that both CLR proteins share conserved characteristics with eukaryotic CLRs, such as an N-terminal helix, a cysteine loop motif and an intracellular loop intermediate in length between the long loops of other eukaryotic CLRs and those of prokaryotic CLRs. Both full-length Alv-a1-pHCl and a truncated form, termed tAlv-a1-pHCl, lacking 37 amino-terminal residues which precede the N-terminal helix, formed functional channels in oocytes. After pH activation tAlv-a1-pHCl showed de-sensitization and was not modulated by ivermectin. In contrast, pH-activated full length Alv-a1-pHCl showed a marked rebound current and was significantly modulated by ivermectin. A thermostability assay indicated that purified tAlv-a1-pHCl expressed in Sf9 cells denatured at higher temperature than the nicotinic-acetylcholine receptor (nAChR) from Torpedo californica.