Molecular characterization of GABA receptor subunits from the parasitic nematode Haemonchus contortus

Haemonchus contortus is a parasitic nematode that is controlled by several nematocides\nwhich target ion channels. We have identified two H. contortus ion channel genes, Hcounc-\n49B and C that encode two GABA-gated chloride channel subunits.\nElectrophysiological analysis shows that the Hco-UNC-49B subunit forms a functional\nhomomeric channel in Xenopus laevis oocytes that produces a robust response to GABA\nand is highly sensitive to picrotoxin. In contrast, Hco-UNC-49C alone does not respond\nto GABA but can assemble with Hco-UNC-49B to form a heteromeric channel with an\nincreased sensitivity to GABA and a lower sensitivity to picrotoxin. To investigate the\nsubunit requirements for high agonist sensitivity, we generated cross-assembled channels\nby co-expressing the H. contortus subunits with UNC-49 subunits from the nematode\nCaenorhabditis elegans (Cel-UNC-49). Co-expressing the Cel-UNC-49B with Hco-\nUNC-49C produced a heteromeric channel with a low sensitivity to GABA. In contrast,\nco-expressing Hco-UNC-49B with Cel-UNC-49C produced a heteromeric channel that\nwas highly sensitive to GABA. These results suggest that the Hco-UNC-49B subunit is\nthe key determinant for the high agonist sensitivity of heteromeric channels.