GABA receptors in Caenorhabditis elegans embryonic muscle cells

GUILLERMINA HERNANDO; CECILIA BOUZAT

Huerta Grande, Córdoba

Congreso; Third Join Meeting of the Argentine Society for Neurosciences and the Argentine Workshop in Neurosciences.; 2011

Argentine Society for Neurosciences

Gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in vertebrates and invertebrates. GABA receptors are the target of anxiolytic, antiepileptic and antispasmodic drugs, as well as of commonly used insecticides and anthelmintics. Here we studied the free-living nematode and model organism Caenorhabditis elegans, which is also a representative member of a large phylum that includes many parasitic members. At the C. elegans neuromuscular junction (NMJ), body wall muscles receive innervations from both cholinergic (excitatory) and GABAergic (inhibitory) motor neurons at en passant synapses along the nerve cord. The appropriate balance of acetylcholine (ACh) and GABA signaling is required for coordinated muscle contraction and movement. One GABA and two ACh receptors function at the C. elegans NMJ. GABA receptor is encoded by the unc-49 gene, which is translated into three subunits (UNC-49A, UNC-49B, and UNC-49C). At the adult stage the GABA receptor is a heteromer composed of the B and C subunits (Bamber et al., 2005), while UNC-49A is almost undetectable at this stage. The two subunits of the UNC-49B/C heteromultimer play different roles; UNC-49B confers synaptic localization and gates the channel and UNC-49C serves a modulatory subunit. The composition of the GABA receptor at larval stages has not been elucidated to date. Furthermore, the GABA agonist muscimol relaxes all the body wall muscles and causes the animal to lengthen in adult stage, but it does not have this effect on L1s. Instead, it can shorten some L1s. To better understand the basic molecular mechanisms of GABA neurotransmission, we are studying GABA receptors at neuromuscular junction of Caenorhabditis elegans of L1 muscle cells. By using a primary culture method that allows differentiation of C. elegans embryonic cells into L1 muscle cells in vitro, we have explored at macroscopic and single-channel levels the properties of the GABAR from C. elegans at this early stage. In the present study we have detected for the first time GABAR activity from L1 stage. The characterization of these receptors in a genetically tractable organism could provide new avenues of exploration for selective drugs acting as modulators of GABA receptors.