Effects of propofol on GABAergic and glutamatergic transmission in isolated hippocampal single nerve-synapse preparations

We evaluated the effects of pi opolol on synaptic transmission using a mechanically dissociated preparation of rat hippocampal CA3 neurons to allow assays of single bouton responses evoked horn retained functional native nerve endings. We studied synaptic and extrasynaptic GABA(A) and glutamate receptor responses in a preparation in which experimental solutions rapidly accessed synaptic terminal Whole-cell responses were evoked by bath application of GABA and glutamate. Synaptic inhibitory and excitatory postsynaptic currents (IPSC and EPSC) were measured as spontaneous and evoked postsynaptic responses. Evoked currents were elicited by focal electrical stimulation. Propofol (1-100 mu M) enhanced extrasynaptic GABA(A)-receptor mediated responses but the increase at clinically relevant concentrations (1 mu M) were minor. In contrast, 1 mu M propofol significantly increased both the amplitude and frequency of spontaneous IPSCs (sIPSCs) and increased the amplitudes of evoked IPSCs (elPSCs) while decreasing failure rates (RD and paired-pulse ratios (PPR). Decay times of sIPSCs and elPSCs were significantly prolonged. Although propolol had no effect on extrasynaptic glutamate responses, only supra-clinical propofol concentrations (>= 10 mu M) increased the spontaneous EPSCs (sEPSCs, amplitudes and frequencies) but suppressed evoked EPSCs (eEPSCs decreased amplitudes with increased RI and PPR). The decay phases of sEPSCs and e EPSCs were not changed. The propofol-induced changes in sEPSCs and eEPSCs resulted from presynaptic GABA(A) receptor-mediated depolarization, because these actions were blocked by bicuculline. These results suggest that propolol acts at presynaptic and postsynaptic GABA(A) receptors within GABAergic synapses, but also increases extrasynaptic GABA responses. Our results expand the locus of propofol actions to GABAergic and glutamatergic synapses. (C) 2013 Elsevier B.V. All rights reserved.