TY - JOUR
T1 - Ketamine inhibits presynaptic and postsynaptic nicotinic excitation of identified cardiac parasympathetic neurons in nucleus ambiguus
AU - Irnaten, Mustapha
AU - Wang, Jijiang
AU - Venkatesan, Priya
AU - Evans, Cory
AU - Kyoung, Kyoung S.
AU - Andresen, Michael C.
AU - Mendelowitz, David
PY - 2002
Y1 - 2002
N2 - Background. Ketamine increases both blood pressure and heart rate, effects commonly thought of as sympathoexcitatory. The authors investigated possible central nervous system actions of ketamine to inhibit cardiac parasympathetic neurons in the brainstem by inhibiting multiple nicotinic excitatory mechanisms. Methods: The authors used a novel in vitro approach to study the effect of ketamine on identified cardiac parasympathetic preganglionic neurons in rat brainstem slices. The cardiac parasympathetic neurons in the nucleus ambiguus were retrogradely prelabeled with the fluorescent tracer by placing rhodamine into the pericardial sac. Dye-labeled neurons were visually identified for patch clamp recording. The effects of ketamine were tested on nicotine-evoked ligand-gated currents and spontaneous glutamatergic miniature synaptic currents (mini) in cardiac parasympathetic preganglionic neurons. Results: Ketamine (10 μM) inhibited (1) the nicotine (1 μM)evoked presynaptic facilitation of glutamate release (mini frequency, 18 ± 7% of control; n = 9), and (2) the direct postsynaptic ligand-gated current (27 ± 8% of control; n = 9), but ketamine did not alter the amplitude of postsynaptic miniature non-N-methyl-D-aspartate currents. α Bungarotoxin, an antagonist of α7 containing nicotinic presynaptic receptors, blocked ketamine actions on mini frequency (n = 10) but not mini amplitude. Conclusions: Ketamine inhibits the presynaptic nicotinic receptors responsible for facilitating neurotransmitter release, as well as the direct ligand-gated inward current, but does not alter the nicotinic augmentation of non-N-methyl-D-aspartate currents in brainstem parasympathetic cardiac neurons. Such actions may mediate the decrease in parasympathetic cardiac activity and increase in heart rate that occurs with ketamine.
AB - Background. Ketamine increases both blood pressure and heart rate, effects commonly thought of as sympathoexcitatory. The authors investigated possible central nervous system actions of ketamine to inhibit cardiac parasympathetic neurons in the brainstem by inhibiting multiple nicotinic excitatory mechanisms. Methods: The authors used a novel in vitro approach to study the effect of ketamine on identified cardiac parasympathetic preganglionic neurons in rat brainstem slices. The cardiac parasympathetic neurons in the nucleus ambiguus were retrogradely prelabeled with the fluorescent tracer by placing rhodamine into the pericardial sac. Dye-labeled neurons were visually identified for patch clamp recording. The effects of ketamine were tested on nicotine-evoked ligand-gated currents and spontaneous glutamatergic miniature synaptic currents (mini) in cardiac parasympathetic preganglionic neurons. Results: Ketamine (10 μM) inhibited (1) the nicotine (1 μM)evoked presynaptic facilitation of glutamate release (mini frequency, 18 ± 7% of control; n = 9), and (2) the direct postsynaptic ligand-gated current (27 ± 8% of control; n = 9), but ketamine did not alter the amplitude of postsynaptic miniature non-N-methyl-D-aspartate currents. α Bungarotoxin, an antagonist of α7 containing nicotinic presynaptic receptors, blocked ketamine actions on mini frequency (n = 10) but not mini amplitude. Conclusions: Ketamine inhibits the presynaptic nicotinic receptors responsible for facilitating neurotransmitter release, as well as the direct ligand-gated inward current, but does not alter the nicotinic augmentation of non-N-methyl-D-aspartate currents in brainstem parasympathetic cardiac neurons. Such actions may mediate the decrease in parasympathetic cardiac activity and increase in heart rate that occurs with ketamine.
UR - http://www.scopus.com/inward/record.url?scp=0036184203&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036184203&partnerID=8YFLogxK
U2 - 10.1097/00000542-200203000-00024
DO - 10.1097/00000542-200203000-00024
M3 - Article
C2 - 11873043
AN - SCOPUS:0036184203
SN - 0003-3022
VL - 96
SP - 667
EP - 674
JO - Anesthesiology
JF - Anesthesiology
IS - 3
ER -