Abstract
The most abundant synapses in the central nervous system of vertebrates are inhibitory synapses that use the neurotransmitter gamma-aminobutyric acid (GABA). GABA is also an important neurotransmitter in C. elegans; however, in contrast to vertebrates where GABA acts at synapses of the central nervous system, in nematodes GABA acts primarily at neuromuscular synapses. Specifically, GABA acts to relax the body muscles during locomotion and foraging and to contract the enteric muscles during defecation. The importance of this neurotransmitter for basic motor functions of the worm has facilitated the genetic analysis of proteins required for GABA function. Genetic screens have identified the GABA biosynthetic enzyme, the vesicular transporter, inhibitory and excitatory receptors, and a transcription factor required for the differentiation of GABA cell identity. The plasma membrane transporter and other GABA receptors have been identified by molecular criteria.
Highlights
Inhibited the crayfish stretch receptor when applied exogenously (Florey, 1953)
GABA's presumed absence in invertebrates was contradicted by the discovery that it was found to be highly concentrated in inhibitory motor neurons of Ascaris (Guastella et al, 1991; Johnson and Stretton, 1987) and crayfish (Kravitz et al, 1963)
GABA receptors are activated by muscimol, whereas GABA receptors are activated by baclofen (Figure 1)
Summary
Electrophysiological recordings from Ascaris by del Castillo demonstrated that GABA application inhibits body muscles by opening chloride channels (Del Castillo et al, 1963). Chloride ions are pumA ped out of the cell; activation of GABA receptors will permit chloride to diffuse into the cell, hyperpolarize the membrane and decrease the excitability of the cell. This type of inhibition is called hyperpolarizing inhibition. Internal chloride is at concentrations higher than the equilibrium potential In these cases, opening chloride channels caused an efflux of this anion, creating an inward current, and depolarizing the membrane. The pharmacology of GABA rBeceptors in C. elegans differs somewhat compared to GABA receptors in vertebrates, nematodes possess both GABA and GABA receptors based on sequence similarity
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