Propofol facilitated excitatory postsynaptic currents frequency on nucleus tractus solitarii (NTS) neurons

Propofol, an intravenous anesthetic, is broadly used for general anesthesia and diagnostic sedations due to its fast onset and recovery. Propofol depresses respiratory and cardiovascular reflex responses, however, their underlying mechanisms are not well known. Cardiorespiratory information from visceral afferent vagus nerves is integrated in the nucleus tractus solitarii (NTS). Cardiac and respiratory signals transducing vagal afferent neurons release the excitatory neurotransmitter glutamate onto NTS neurons in an activity dependent manner and trigger negative feedback reflex responses. In this experiment, the effects of propofol on glutamatergic synaptic responses at NTS neurons was tested using patch clamp methods. Glutamatergic excitatory postsynaptic currents (EPSC) were recorded at chloride reversal potential (− 49 mV) without γ-aminobutyric acid type A (GABAA) receptor antagonists. Propofol (≥ 3 μM) facilitated frequency of the spontaneous EPSCs in a concentration dependent manner without altering amplitude and decay time. The GABAA receptor selective antagonist, gabazine (6 μM), attenuated propofol effects on glutamate release. Propofol (10 μM) evoked glutamate release was also blocked in the presence of the voltage dependent Na+ and Ca2+ channel blockers TTX (0.3 μM) and Cd2+ (0.2 mM), respectively. In addition, the Na+–K+–Cl− cotransporter type 1 antagonist bumetanide (10 μM) also inhibited propofol evoked increase in sEPSC frequency. These results suggest that propofol evoked glutamate release onto NTS neurons by GABAA receptor-mediated depolarization of the presynaptic excitatory terminals.

► Propofol effects on acutely isolated nucleus tractus solitarii neuron were tested. ► Propofol facilitated frequency of the EPSCs in a concentration dependent manner. ► The GABAA receptor selective antagonist, gabazine, attenuated propofol effects. ► Propofol evoked glutamate release was also blocked by TTX and Cd2+. ► Na–K–Cl cotransporter antagonist also blocked propofol evoked frequency increase.