γ-aminobutyric acid (GABA) plays many of its key roles in embryonic development and functioning of the central nervous
system (CNS) by acting on ligand gated chloride-permeable channels known as GABAA receptors (GABAAR). Classically, GABAARmediated
synaptic communication is tailored to allow rapid and precise transmission of information to synchronize the activity of large
populations of cells to generate and maintain neuronal networks oscillations. An alternative type of inhibition mediated by GABAA receptors,
initially described about 25 years ago, is characterized by a tonic activation of receptors that react to ambient extracellular
GABA. The receptors that mediate this action are wide-spread throughout the nerve cells but are located distant from the sites of GABA
release, and therefore they have been called extrasynaptic GABAA receptors. The molecular nature of the extrasynaptic GABAA receptors
and the tonic inhibitory current they generate have been characterized in many brain structures, and due to its relevance in controlling
neuron excitability they have become attractive pharmacological targets for a variety of neurological disorders such as schizophrenia, epilepsy
and Parkinson disease. In the spinal cord, early studies have implicated these receptors in anesthesia, chronic pain, motor control,
and locomotion. This review highlights past and present developments in the field of extrasynaptic GABAA receptors and emphasizes
their subunit containing distribution and physiological role in the spinal cord.
Keywords: Spinal cord, GABA, extrasynaptic GABAA receptors, motoneurons, primary afferent fibers.
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