Tonic GABAA receptor conductance in medial subnucleus of the tractus solitarius neurons is inhibited by activation of μ-opioid receptors

Herman MA, Gillis RA, Vicini S, Dretchen KL, Sahibzada N. Tonic GABA(A) receptor conductance in medial subnucleus of the tractus solitarius neurons is inhibited by activation of mu-opioid receptors. J Neurophysiol 107: 1022-1031, 2012. First published November 23, 2011; doi: 10.1152/jn.00853.2011.-Our laboratory previously reported that gastric activity is controlled by a robust GABA A receptor-mediated inhibition in the medial nucleus of the tractus solitarius (mNTS) (Herman et al. 2009), and that mu-opioid receptor activation inhibits gastric tone by suppression of this GABA signaling (Herman et al. 2010). These data raised two questions: 1) whether any of this inhibition was due to tonic GABA(A) receptor-mediated conductance in the mNTS; and 2) whether mu-opioid receptor activation suppressed both tonic and phasic GABA signaling. In whole cell recordings from rat mNTS neurons, application of three GABA(A) receptor antagonists (gabazine, bicuculline, and picrotoxin) produced a persistent reduction in holding current and decrease in population variance or root mean square (RMS) noise, suggesting a blockade of tonic GABA signaling. Application of gabazine at a lower concentration abolished phasic currents, but had no effect on tonic currents or RMS noise. Application of the delta-subunit preferring agonist gaboxadol (THIP) produced a dose-dependent persistent increase in holding current and RMS noise. Pretreatment with tetrodotoxin prevented the action of gabazine, but had no effect on the THIP-induced current. Membrane excitability was unaffected by the selective blockade of phasic inhibition, but was increased by blockade of both phasic and tonic currents. In contrast, activation of tonic currents decreased membrane excitability. Application of the mu-opioid receptor agonist DAMGO produced a persistent reduction in holding current that was not observed following pretreatment with a GABA(A) receptor antagonist and was not evident in mice lacking the delta-subunit. These data suggest that mNTS neurons possess a robust tonic inhibition that is mediated by GABA(A) receptors containing the delta-subunit, that determines membrane excitability, and that is partially regulated by mu-opioid receptors.