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

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.

Name thesis:degree_name

Master of Science (MSc)

Discipline thesis:degree_discipline

Applied Bioscience

Grantor

University of Ontario Institute of Technology

Year dc:date.issued

2009

Author dc:creator

• Siddiqui, Salma

Advisors dc:contributor.advisor

• Forrester, Sean
• Bonetta, Dario

• GABA
• Ligand-gated chloride channel
• Electrophysiology
• Homomeric channel
• Haemonchus contortus
• Heteromeric channel

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10155/31

OAI identifier oai:identifier

oai:ontariotechu.scholaris.ca:10155/31