Major role of GABAA-receptor mediated tonic inhibition in propofol suppression of supraoptic magnocellular neurons

Using slice patch clamp recording, we examined the effects of general anesthetic propofol (2,6-diisoprophlphenol) on dual modality of GABAA inhibition in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs): conventional quantal synaptic transmission (IPSCs, Iphasic) and persistent tonic form of inhibitory current (Itonic). Propofol (10 μM) enhanced Itonic as shown by an inward shift in Iholding (16.46 ± 2.93 pA, n = 27) and RMS increase (from 3.37 ± 0.21 pA to 4.68 ± 0.33 pA, n = 27) in SON MNCs. Propofol also prolonged the decay time of IPSCs with decreased IPSCs frequency but no significant changes in IPSCs amplitude. Overall, propofol (1–10 μM) caused much smaller increase in mean Iphasic than mean Itonic at all tested concentrations. In consistent with the enhancement of GABAA currents, propofol attenuated ongoing firing activities of SON MNCs by ∼65% of control. Selective inhibition of Iphasic by a GABAA antagonist, gabazine (1 μM), failed to block the propofol suppression of the firing activities, while inhibition of Itonic and Iphasic by bicuculline (20 μM) efficiently blocked the propofol-induced neurodepression in SON MNCs. Taken together, our results showed that propofol facilitated Itonic with marginal increase in mean Iphasic, and this could be a mechanism reducing the intrinsic SON MNCs excitability during propofol anesthesia.

► Propofol enhances tonic as well as phasic GABAA inhibition in SON neurons.
► Propofol increases Cl− charge transfer mainly via tonic GABAA currents in SON MNCs.
► Propofol induces neurodepression dominantly via tonic GABAA inhibition in SON MNCs.