Allosteric modulation of ligand gated ion channels by ivermectin.

摘要: Ivermectin acts as a positive allosteric regulator of several ligand-gated channels including the glutamate-gated chloride channel (GluCl), gamma aminobutyric acid type-A receptor, glycine neuronal alpha7-nicotinic receptor and purinergic P2X4 receptor. In most ivermectin-sensitive channels, effects ivermectin include potentiation agonist-induced currents at low concentrations opening higher concentrations. Based on mutagenesis, electrophysiological recordings functional analysis chimeras between ivermectin-insensitive receptors, it has been concluded that by insertion transmembrane helices. The three-dimensional structure C. elegans GluCl complexed with revealed details ivermectin-binding site, however, no generic motif amino acids could accurately predict binding site for other ligand gated channels. Here, we will review what is currently known about modulation Cys-loop family ion are critical structural determinants underlying channel.