Tonic GABAergic Inhibition of Sympathetic Preganglionic Neurons: A Novel Substrate for Sympathetic Control

Abstract

The sympathetic tone is primarily defined by the level of activity of the sympathetic preganglionic neurons. We report a novel inhibitory influence on sympathetic activity, that of tonic GABAergic inhibition which could have a profound global effect on sympathetic outflow. Recording from identified SPNs in the intermediolateral cell column (IML) of rat spinal cord slices, application of the GABA receptor antagonist bicuculline, but not gabazine, elicited a change in voltage that lasted for the duration of application. This response was mediated by a direct effect on SPNs since it persisted in tetrodotoxin and low Ca(2+)/high Mg(2+) and the amplitude of responses were related to Cl(-) concentration in patch solutions. Such tonic inhibitory responses were not observed in interneurons, the other neuronal type in the IML, although ongoing IPSPs were antagonized in these neurons. The effects of bicuculline were enhanced by diazepam but not zolpidem or the GABA modulators THIP and THDOC suggesting a role for alpha5 subunits. PCR using primers for the alpha5 and delta subunits indicated the presence of alpha5, but not delta subunits in the IML. Firing rates of SPNs were enhanced by bicuculline and decreased by diazepam indicating that this tonic inhibition has a profound effect on the excitability of SPNs. These data indicate a novel influence for controlling the activity of SPNs regardless of their function.