Extrasynaptic GABAA Receptors in the Brainstem and Spinal Cord: Structure and Function

Rodolfo      Delgado-Lezama; Emanuel      Loeza-Alcocer; Carmen      Andres; Justo      Aguilar; Pierre   A.   Guertin; Ricardo      Felix

doi:10.2174/1381612811319240013

Abstract

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 GABA_A receptors (GABA_AR). Classically, GABA_ARmediated 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 GABA_A 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 GABA_A receptors. The molecular nature of the extrasynaptic GABA_A 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 GABA_A receptors and emphasizes their subunit containing distribution and physiological role in the spinal cord.

Keywords: Spinal cord, GABA, extrasynaptic GABA_A receptors, motoneurons, primary afferent fibers.

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