Tonic inhibition in spinal ventral horn interneurons mediated by α 5 subunit-containing GABA A receptors

Abstract

GABA A receptors mediate synaptic and tonic inhibition in many neurons of the central nervous system. These receptors can be constructed from a range of different subunits deriving from seven identified families. Among these subunits, α 5 has been shown to mediate GABAergic tonic inhibitory currents in neurons from supraspinal nuclei. Likewise, immunohistochemical and in situ hybridization studies have shown the presence of the α 5 subunit in spinal cord neurons, though almost nothing is known about its function. In the present report, using slices of the adult turtle spinal cord as a model system we have recorded a tonic inhibitory current in ventral horn interneurons (VHIs) and determined the functional contribution of the α 5 subunit-containing GABA A receptors to this current. Patch clamp studies show that the GABAergic tonic inhibitory current in VHIs is not affected by the application of antagonists of the α 4/6 subunit-containing GABA A receptors, but is sensitive to L-655708, an antagonist of the GABA A receptors containing α 5 subunits. Last, by using RT-PCR and immunohistochemistry we confirmed the expression of the α 5 subunit in the turtle spinal cord. Together, these results suggest that GABA A receptors containing the α 5 subunit mediate the tonic inhibitory currents observed in VHIs.