Propofol modulates γ-aminobutyric acid-mediated inhibitory neurotransmission to cardiac vagal neurons in the nucleus ambiguus

Background: Although it is well recognized that anesthetics modulate the central control of cardiorespiratory homeostasis, the cellular mechanisms by which anesthetics alter cardiac parasympathetic activity are poorly understood. One common site of action of anesthetics is inhibitory neurotransmission. This study investigates the effect of propofol on gamma-aminobutyric acid-mediated (GABAergic) and glycinergic neurotransmission to cardiac parasympathetic neurons. Methods: Cardiac parasympathetic neurons were identified in vitro by the presence of a retrograde fluorescent tracer, and spontaneous GABAergic and glycinergic synaptic currents were examined using whole cell patch clamp techniques. Results: Propofol at concentrations of 1.0 mum and greater significantly (P < 0.05) increased the duration and decay time of spontaneous GABAergic inhibitory postsynaptic currents. To determine whether the action of propofol was at presynaptic or postsynaptic sites, tetrodotoxin was applied to isolate miniature inhibitory postsynaptic currents. Propofol at concentrations of 1.0 muM and greater significantly (P < 0.05) prolonged the decay time and duration of miniature inhibitory postsynaptic currents, indicating that propofol directly alters GABAergic neurotransmission at a postsynaptic site. Propofol at high concentrations (greater than or equal to 50 muM) also inhibited the frequency of both GABAergic inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents. Propofol at concentrations up to 50 muM had no effect on glycinergic neurotransmission. Conclusions: Propofol may vary heart rate by modulating GABAergic neurotransmission to cardiac parasympathetic neurons. At clinically relevant concentrations ( greater than or equal to 1.0 muM), propofol facilitated GABAergic responses in cardiac vagal neurons by increasing decay time, which would increase inhibition of cardioinhibitory cardiac vagal neurons and evoke an increase in heart rate. At higher supraclinical concentrations (greater than or equal to 50 muM), propofol inhibits GABAergic neurotransmission to cardiac vagal neurons, which would evoke a decrease in heart rate.