The pentameric ligand-gated ion channels (pLGICs) are ionotropic neurotransmitter receptors that mediate electrical signaling at chemical synapses. The X-ray structures of two prokaryotic homologues have provided first insight into the detailed architecture of the family at high resolution [1]. The structure of GLIC, a proton-activated channel from the cyanobacterium Gloebacter violaceous shows an open conformation of the pore [2]. The channel conducts cations with similar properties as the nicotinic acetylcholine receptor (nAChR). The transmembrane pore is funnel-shaped with a wide hydrophobic entrance at the extracellular side that narrows to a hydrophilic intracellular opening. In this region conserved residues coordinate ions which have lost a large part of their hydration shell [3]. The structure of ELIC, a pLGIC from the plant pathogen Erwinia chrysanthemi, shows a non-conducting conformation that was obtained in the absence of ligands [4]. In its structure the extracellular half of the pore is occluded by bulky hydrophobic residues that likely prevent ion conduction. ELIC is activated by a set of primary amines that include the neurotransmitter GABA [5]. The protein forms cation selective channels with large conductance that slowly desensitize in the presence of ligands. Both proteins were used to study distinct mechanisms of channel inhibition. Ion conduction in GLIC is inhibited by the same set of open channel blockers that also act on nAchRs [3]. In ELIC acetylcholine acts as competitive inhibitor, which binds to the agonist site and stabilizes the closed conformation of the channel. Divalent cations, in contrast, are allosteric modulators, which bind to a site distant from the agonist binding site where they interfere with gating [6]. The strong structural similarity to their eukaryotic counterparts make ELIC and GLIC important model systems for the pLGIC family that will ultimately allow a detailed comprehension of mechanistic properties that are still poorly understood.