摘要
Recent reports have suggested that various general anesthetics affect presynaptic processes in the central nervous system. However, characterizations of the influence of intravenous anesthetics on neurotransmitter release from presynaptic nerve terminals (boutons) are insufficient. Because the presynaptic calcium concentration ([Ca<sup>2+</sup>]<sub>pre</sub>) regulates neurotransmitter release, we investigate the effects of the intravenous anesthetic propofol on neurotransmitter release by measuring [Ca<sup>2+</sup>]<sub>pre</sub> in the presynaptic boutons of individual dissociated hippocampal neurons. Brain slices were prepared from Sprague–Dawley rats (10 - 14 days of age). The hippocampal CA1 area was isolated with a fire-polished glass pipette, which vibrated horizontally to dissociate hippocampal CA1 neurons along with their attached presynaptic boutons. Presynaptic boutons were visualized under a confocal laser scanning microscope after staining with FM1-43 dye, and [Ca<sup>2+</sup>]<sub>pre</sub> was measured using fluo-3 AM dye. Glutamate (3 – 100 μM) administration increased [Ca2+]<sub>pre</sub> in Ca<sup>2+-</sup> containing external solution in a concentration-dependent manner. Propofol (3 – 30 μM) dose-dependently suppressed this glutamate (30 μM)-induced increase in [Ca<sup>2+</sup>]<sub>pre</sub> in boutons attached to dendrites, but not to the soma or base of the dendritic tree. The large majority of excitatory synapses on CA1 neurons are located on dendritic spines;therefore, propofol may affect glutamate-induced Ca<sup>2+</sup> mobilization in excitatory, but not inhibitory, presynaptic boutons. Propofol may possibly have some effect on glutamate-regulated neurotransmitter release from excitatory presynaptic nerve terminals through inhibiting the increase in [Ca<sup>2+</sup>]<sub>pre</sub> induced by glutamate.
Recent reports have suggested that various general anesthetics affect presynaptic processes in the central nervous system. However, characterizations of the influence of intravenous anesthetics on neurotransmitter release from presynaptic nerve terminals (boutons) are insufficient. Because the presynaptic calcium concentration ([Ca<sup>2+</sup>]<sub>pre</sub>) regulates neurotransmitter release, we investigate the effects of the intravenous anesthetic propofol on neurotransmitter release by measuring [Ca<sup>2+</sup>]<sub>pre</sub> in the presynaptic boutons of individual dissociated hippocampal neurons. Brain slices were prepared from Sprague–Dawley rats (10 - 14 days of age). The hippocampal CA1 area was isolated with a fire-polished glass pipette, which vibrated horizontally to dissociate hippocampal CA1 neurons along with their attached presynaptic boutons. Presynaptic boutons were visualized under a confocal laser scanning microscope after staining with FM1-43 dye, and [Ca<sup>2+</sup>]<sub>pre</sub> was measured using fluo-3 AM dye. Glutamate (3 – 100 μM) administration increased [Ca2+]<sub>pre</sub> in Ca<sup>2+-</sup> containing external solution in a concentration-dependent manner. Propofol (3 – 30 μM) dose-dependently suppressed this glutamate (30 μM)-induced increase in [Ca<sup>2+</sup>]<sub>pre</sub> in boutons attached to dendrites, but not to the soma or base of the dendritic tree. The large majority of excitatory synapses on CA1 neurons are located on dendritic spines;therefore, propofol may affect glutamate-induced Ca<sup>2+</sup> mobilization in excitatory, but not inhibitory, presynaptic boutons. Propofol may possibly have some effect on glutamate-regulated neurotransmitter release from excitatory presynaptic nerve terminals through inhibiting the increase in [Ca<sup>2+</sup>]<sub>pre</sub> induced by glutamate.
