title: Propofol modulates gamma-aminobutyric acid-mediated inhibitory neurotransmission to cardiac vagal neurons in the nucleus ambiguus.
abstract: 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 microm 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 microm 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 (> or =50 microm) also inhibited the frequency of both GABAergic inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents. Propofol at concentrations up to 50 microm had no effect on glycinergic neurotransmission.
  
  
  CONCLUSIONS
  Propofol may vary heart rate by modulating GABAergic neurotransmission to cardiac parasympathetic neurons. At clinically relevant concentrations (> or =1.0 microm), 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 (> or =50 microm), propofol inhibits GABAergic neurotransmission to cardiac vagal neurons, which would evoke a decrease in heart rate.
authors.affiliation: Department of Pharmacology, George Washington University, Washington, D.C., USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Zheng-Gui
authors.initials: ZG
authors.lastname: Huang
authors.forename: Allison
authors.initials: A
authors.lastname: Gold
authors.forename: Evguenia
authors.initials: E
authors.lastname: Bouairi
authors.forename: Cory
authors.initials: C
authors.lastname: Evans
authors.forename: Michael C
authors.initials: MC
authors.lastname: Andresen
authors.forename: David
authors.initials: D
authors.lastname: Mendelowitz
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D005680:gamma-Aminobutyric Acid; D015742:Propofol