Ketamine differentially blocks sensory afferent synaptic transmission in medial nucleus tractus solitarius (mNTS)

Young Ho Jin, Timothy W. Bailey, Mark W. Doyle, Bai yan Li, Kyoung S K Chang, John H. Schild, David Mendelowitz, Michael Andresen

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background: Ketamine increases blood pressure and heart rate by unknown mechanisms, but studies suggest that an intact central nervous system and arterial baroreceptors are required. In the brain stem, medial nucleus tractus solitarius receives afferents from nodose neurons that initiate cardiovascular autonomic reflexes. Here, the authors assessed ketamine actions on afferent medial nucleus tractus solitarius synaptic transmission. Methods: Ketamine was applied to horizontally sliced brain stems. Solitary tract (ST) stimulation evoked excitatory postsynaptic currents (eEPSCs) in medial nucleus tractus solitarius neurons. Capsaicin (200 nM) block of ST eEPSCs sorted neurons into sensitive (n = 19) and resistant (n = 23). In nodose ganglion slices, shocks to the peripheral vagal trunk activated afferent action potentials in sensory neurons classified by conduction velocities and capsaicin. Results: Ketamine potently (10-100 μM) blocked small, ST-evoked N-methyl-D-aspartate synaptic currents found only in a subset of capsaicin-resistant neurons (6 of 12). Surprisingly, ketamine reversibly inhibited ST eEPSC amplitudes and induced synaptic failure at lower concentrations in capsaicin-sensitive than in capsaicin-resistant neurons (P <0.005; n = 11 and 11). Spontaneous EPSCs using non-N-methyl-D-aspartate receptors were insensitive even to 1-3 mM ketamine, suggesting that ST responses were blocked presynaptically. Similarly, ketamine blocked C-type action potential conduction at lower concentrations than A-type nodose sensory neurons. Conclusion: The authors conclude that ketamine inhibits postsynaptic N-methyl-D-aspartate receptors and presynaptic afferent processes in medial nucleus tractus solitarius. Unexpectedly, capsaicin-sensitive (C-type), unmyelinated afferents are significantly more susceptible to block than capsaicin-resistant (A-type), myelinated afferents. This differentiation may be related to tetrodotoxin-resistant sodium currents. Since C-type afferents mediate powerful arterial baroreflexes effects, these differential actions may contribute to ketamine-induced cardiovascular dysfunction.

Original languageEnglish (US)
Pages (from-to)121-132
Number of pages12
JournalAnesthesiology
Volume98
Issue number1
DOIs
StatePublished - Jan 1 2003

Fingerprint

Solitary Nucleus
Ketamine
Synaptic Transmission
Capsaicin
Excitatory Postsynaptic Potentials
Neurons
Sensory Receptor Cells
Action Potentials
Brain Stem
Nodose Ganglion
D-Aspartic Acid
Afferent Neurons
Pressoreceptors
Baroreflex
Tetrodotoxin
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Reflex
Shock
Central Nervous System

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Ketamine differentially blocks sensory afferent synaptic transmission in medial nucleus tractus solitarius (mNTS). / Jin, Young Ho; Bailey, Timothy W.; Doyle, Mark W.; Li, Bai yan; Chang, Kyoung S K; Schild, John H.; Mendelowitz, David; Andresen, Michael.

In: Anesthesiology, Vol. 98, No. 1, 01.01.2003, p. 121-132.

Research output: Contribution to journalArticle

Jin, Young Ho ; Bailey, Timothy W. ; Doyle, Mark W. ; Li, Bai yan ; Chang, Kyoung S K ; Schild, John H. ; Mendelowitz, David ; Andresen, Michael. / Ketamine differentially blocks sensory afferent synaptic transmission in medial nucleus tractus solitarius (mNTS). In: Anesthesiology. 2003 ; Vol. 98, No. 1. pp. 121-132.
@article{695b70d57d1a49d8b33d120b39da4411,
title = "Ketamine differentially blocks sensory afferent synaptic transmission in medial nucleus tractus solitarius (mNTS)",
abstract = "Background: Ketamine increases blood pressure and heart rate by unknown mechanisms, but studies suggest that an intact central nervous system and arterial baroreceptors are required. In the brain stem, medial nucleus tractus solitarius receives afferents from nodose neurons that initiate cardiovascular autonomic reflexes. Here, the authors assessed ketamine actions on afferent medial nucleus tractus solitarius synaptic transmission. Methods: Ketamine was applied to horizontally sliced brain stems. Solitary tract (ST) stimulation evoked excitatory postsynaptic currents (eEPSCs) in medial nucleus tractus solitarius neurons. Capsaicin (200 nM) block of ST eEPSCs sorted neurons into sensitive (n = 19) and resistant (n = 23). In nodose ganglion slices, shocks to the peripheral vagal trunk activated afferent action potentials in sensory neurons classified by conduction velocities and capsaicin. Results: Ketamine potently (10-100 μM) blocked small, ST-evoked N-methyl-D-aspartate synaptic currents found only in a subset of capsaicin-resistant neurons (6 of 12). Surprisingly, ketamine reversibly inhibited ST eEPSC amplitudes and induced synaptic failure at lower concentrations in capsaicin-sensitive than in capsaicin-resistant neurons (P <0.005; n = 11 and 11). Spontaneous EPSCs using non-N-methyl-D-aspartate receptors were insensitive even to 1-3 mM ketamine, suggesting that ST responses were blocked presynaptically. Similarly, ketamine blocked C-type action potential conduction at lower concentrations than A-type nodose sensory neurons. Conclusion: The authors conclude that ketamine inhibits postsynaptic N-methyl-D-aspartate receptors and presynaptic afferent processes in medial nucleus tractus solitarius. Unexpectedly, capsaicin-sensitive (C-type), unmyelinated afferents are significantly more susceptible to block than capsaicin-resistant (A-type), myelinated afferents. This differentiation may be related to tetrodotoxin-resistant sodium currents. Since C-type afferents mediate powerful arterial baroreflexes effects, these differential actions may contribute to ketamine-induced cardiovascular dysfunction.",
author = "Jin, {Young Ho} and Bailey, {Timothy W.} and Doyle, {Mark W.} and Li, {Bai yan} and Chang, {Kyoung S K} and Schild, {John H.} and David Mendelowitz and Michael Andresen",
year = "2003",
month = "1",
day = "1",
doi = "10.1097/00000542-200301000-00021",
language = "English (US)",
volume = "98",
pages = "121--132",
journal = "Anesthesiology",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Ketamine differentially blocks sensory afferent synaptic transmission in medial nucleus tractus solitarius (mNTS)

AU - Jin, Young Ho

AU - Bailey, Timothy W.

AU - Doyle, Mark W.

AU - Li, Bai yan

AU - Chang, Kyoung S K

AU - Schild, John H.

AU - Mendelowitz, David

AU - Andresen, Michael

PY - 2003/1/1

Y1 - 2003/1/1

N2 - Background: Ketamine increases blood pressure and heart rate by unknown mechanisms, but studies suggest that an intact central nervous system and arterial baroreceptors are required. In the brain stem, medial nucleus tractus solitarius receives afferents from nodose neurons that initiate cardiovascular autonomic reflexes. Here, the authors assessed ketamine actions on afferent medial nucleus tractus solitarius synaptic transmission. Methods: Ketamine was applied to horizontally sliced brain stems. Solitary tract (ST) stimulation evoked excitatory postsynaptic currents (eEPSCs) in medial nucleus tractus solitarius neurons. Capsaicin (200 nM) block of ST eEPSCs sorted neurons into sensitive (n = 19) and resistant (n = 23). In nodose ganglion slices, shocks to the peripheral vagal trunk activated afferent action potentials in sensory neurons classified by conduction velocities and capsaicin. Results: Ketamine potently (10-100 μM) blocked small, ST-evoked N-methyl-D-aspartate synaptic currents found only in a subset of capsaicin-resistant neurons (6 of 12). Surprisingly, ketamine reversibly inhibited ST eEPSC amplitudes and induced synaptic failure at lower concentrations in capsaicin-sensitive than in capsaicin-resistant neurons (P <0.005; n = 11 and 11). Spontaneous EPSCs using non-N-methyl-D-aspartate receptors were insensitive even to 1-3 mM ketamine, suggesting that ST responses were blocked presynaptically. Similarly, ketamine blocked C-type action potential conduction at lower concentrations than A-type nodose sensory neurons. Conclusion: The authors conclude that ketamine inhibits postsynaptic N-methyl-D-aspartate receptors and presynaptic afferent processes in medial nucleus tractus solitarius. Unexpectedly, capsaicin-sensitive (C-type), unmyelinated afferents are significantly more susceptible to block than capsaicin-resistant (A-type), myelinated afferents. This differentiation may be related to tetrodotoxin-resistant sodium currents. Since C-type afferents mediate powerful arterial baroreflexes effects, these differential actions may contribute to ketamine-induced cardiovascular dysfunction.

AB - Background: Ketamine increases blood pressure and heart rate by unknown mechanisms, but studies suggest that an intact central nervous system and arterial baroreceptors are required. In the brain stem, medial nucleus tractus solitarius receives afferents from nodose neurons that initiate cardiovascular autonomic reflexes. Here, the authors assessed ketamine actions on afferent medial nucleus tractus solitarius synaptic transmission. Methods: Ketamine was applied to horizontally sliced brain stems. Solitary tract (ST) stimulation evoked excitatory postsynaptic currents (eEPSCs) in medial nucleus tractus solitarius neurons. Capsaicin (200 nM) block of ST eEPSCs sorted neurons into sensitive (n = 19) and resistant (n = 23). In nodose ganglion slices, shocks to the peripheral vagal trunk activated afferent action potentials in sensory neurons classified by conduction velocities and capsaicin. Results: Ketamine potently (10-100 μM) blocked small, ST-evoked N-methyl-D-aspartate synaptic currents found only in a subset of capsaicin-resistant neurons (6 of 12). Surprisingly, ketamine reversibly inhibited ST eEPSC amplitudes and induced synaptic failure at lower concentrations in capsaicin-sensitive than in capsaicin-resistant neurons (P <0.005; n = 11 and 11). Spontaneous EPSCs using non-N-methyl-D-aspartate receptors were insensitive even to 1-3 mM ketamine, suggesting that ST responses were blocked presynaptically. Similarly, ketamine blocked C-type action potential conduction at lower concentrations than A-type nodose sensory neurons. Conclusion: The authors conclude that ketamine inhibits postsynaptic N-methyl-D-aspartate receptors and presynaptic afferent processes in medial nucleus tractus solitarius. Unexpectedly, capsaicin-sensitive (C-type), unmyelinated afferents are significantly more susceptible to block than capsaicin-resistant (A-type), myelinated afferents. This differentiation may be related to tetrodotoxin-resistant sodium currents. Since C-type afferents mediate powerful arterial baroreflexes effects, these differential actions may contribute to ketamine-induced cardiovascular dysfunction.

UR - http://www.scopus.com/inward/record.url?scp=0037217821&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037217821&partnerID=8YFLogxK

U2 - 10.1097/00000542-200301000-00021

DO - 10.1097/00000542-200301000-00021

M3 - Article

C2 - 12502988

AN - SCOPUS:0037217821

VL - 98

SP - 121

EP - 132

JO - Anesthesiology

JF - Anesthesiology

SN - 0003-3022

IS - 1

ER -