Molecular characterization of GABA receptor subunits from the parasitic nematode Haemonchus contortus
Date
2009-08-01
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Abstract
Haemonchus contortus is a parasitic nematode that is controlled by several nematocides
which target ion channels. We have identified two H. contortus ion channel genes, Hcounc-
49B and C that encode two GABA-gated chloride channel subunits.
Electrophysiological analysis shows that the Hco-UNC-49B subunit forms a functional
homomeric channel in Xenopus laevis oocytes that produces a robust response to GABA
and is highly sensitive to picrotoxin. In contrast, Hco-UNC-49C alone does not respond
to GABA but can assemble with Hco-UNC-49B to form a heteromeric channel with an
increased sensitivity to GABA and a lower sensitivity to picrotoxin. To investigate the
subunit requirements for high agonist sensitivity, we generated cross-assembled channels
by co-expressing the H. contortus subunits with UNC-49 subunits from the nematode
Caenorhabditis elegans (Cel-UNC-49). Co-expressing the Cel-UNC-49B with Hco-
UNC-49C produced a heteromeric channel with a low sensitivity to GABA. In contrast,
co-expressing Hco-UNC-49B with Cel-UNC-49C produced a heteromeric channel that
was highly sensitive to GABA. These results suggest that the Hco-UNC-49B subunit is
the key determinant for the high agonist sensitivity of heteromeric channels.
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Keywords
GABA, Ligand-gated chloride channel, Electrophysiology, Homomeric channel, Haemonchus contortus, Heteromeric channel