Ketamine-mediated afferent-specific presynaptic transmission blocks in low-threshold and sex-specific subpopulation of myelinated ah-type baroreceptor neurons of rats

Lu Qi Wang, Sheng Zhi Liu, Xin Wen, Di Wu, Lei Yin, Yao Fan, Ye Wang, Wei Ran Chen, Pei Chen, Yang Liu, Xiao Long Lu, Hong Li Sun, Weinian Shou, Guo Fen Qiao, Bai Yan Li

Research output: Contribution to journalArticle

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Abstract

Background: Ketamine enhances autonomic activity, and unmyelinated C-type baroreceptor afferents are more susceptible to be blocked by ketamine than myelinated A-types. However, the presynaptic transmission block in low-threshold and sex-specific myelinated Ah-type baroreceptor neurons (BRNs) is not elucidated. Methods: Action potentials (APs) and excitatory post-synaptic currents (EPSCs) were investigated in BRNs/barosensitive neurons identified by conduction velocity (CV), capsaicin-conjugated with Iberiotoxin-sensitivity and fluorescent dye using intact nodose slice and brainstem slice in adult female rats. The expression of mRNA and targeted protein for NMDAR1 was also evaluated. Results: Ketamine time-dependently blocked afferent CV in Ah-types in nodose slice with significant changes in AP discharge. The concentration-dependent inhibition of ketamine on AP discharge profiles were also assessed and observed using isolated Ah-type BRNs with dramatic reduction in neuroexcitability. In brainstem slice, the 2nd-order capsaicin-resistant EPSCs were identified and ~50% of them were blocked by ketamine concentration-dependently with IC50 estimated at 84.4 μM compared with the rest (708.2 μM). Interestingly, the peak, decay time constant, and area under curve of EPSCs were significantly enhanced by 100 nM iberiotoxin in ketamine-more sensitive myelinated NTS neurons (most likely Ah-types), rather than ketamine-less sensitive ones (A-types). Conclusions: These data have demonstrated, for the first time, that low-threshold and sex-specific myelinated Ah-type BRNs in nodose and Ah-type barosensitive neurons in NTS are more susceptible to ketamine and may play crucial roles in not only mean blood pressure regulation but also buffering dynamic changes in pressure, as well as the ketamine-mediated cardiovascular dysfunction through sexual-dimorphic baroreflex afferent pathway.

Original languageEnglish (US)
Pages (from-to)44108-44122
Number of pages15
JournalOncotarget
Volume6
Issue number42
DOIs
StatePublished - 2015

Fingerprint

Pressoreceptors
Ketamine
Neurons
Action Potentials
Capsaicin
Brain Stem
Afferent Pathways
Baroreflex
Fluorescent Dyes
Inhibitory Concentration 50
Area Under Curve
Blood Pressure
Pressure
Messenger RNA

Keywords

  • Baroreflex afferent pathway
  • Ketamine (KET)
  • Nodose ganglia (NG)
  • Nucleus of the solitary tract (NTS)
  • Pathology section
  • Presynaptic neurotransmission

ASJC Scopus subject areas

  • Oncology

Cite this

Ketamine-mediated afferent-specific presynaptic transmission blocks in low-threshold and sex-specific subpopulation of myelinated ah-type baroreceptor neurons of rats. / Wang, Lu Qi; Liu, Sheng Zhi; Wen, Xin; Wu, Di; Yin, Lei; Fan, Yao; Wang, Ye; Chen, Wei Ran; Chen, Pei; Liu, Yang; Lu, Xiao Long; Sun, Hong Li; Shou, Weinian; Qiao, Guo Fen; Li, Bai Yan.

In: Oncotarget, Vol. 6, No. 42, 2015, p. 44108-44122.

Research output: Contribution to journalArticle

Wang, LQ, Liu, SZ, Wen, X, Wu, D, Yin, L, Fan, Y, Wang, Y, Chen, WR, Chen, P, Liu, Y, Lu, XL, Sun, HL, Shou, W, Qiao, GF & Li, BY 2015, 'Ketamine-mediated afferent-specific presynaptic transmission blocks in low-threshold and sex-specific subpopulation of myelinated ah-type baroreceptor neurons of rats', Oncotarget, vol. 6, no. 42, pp. 44108-44122. https://doi.org/10.18632/oncotarget.6586
Wang, Lu Qi ; Liu, Sheng Zhi ; Wen, Xin ; Wu, Di ; Yin, Lei ; Fan, Yao ; Wang, Ye ; Chen, Wei Ran ; Chen, Pei ; Liu, Yang ; Lu, Xiao Long ; Sun, Hong Li ; Shou, Weinian ; Qiao, Guo Fen ; Li, Bai Yan. / Ketamine-mediated afferent-specific presynaptic transmission blocks in low-threshold and sex-specific subpopulation of myelinated ah-type baroreceptor neurons of rats. In: Oncotarget. 2015 ; Vol. 6, No. 42. pp. 44108-44122.
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abstract = "Background: Ketamine enhances autonomic activity, and unmyelinated C-type baroreceptor afferents are more susceptible to be blocked by ketamine than myelinated A-types. However, the presynaptic transmission block in low-threshold and sex-specific myelinated Ah-type baroreceptor neurons (BRNs) is not elucidated. Methods: Action potentials (APs) and excitatory post-synaptic currents (EPSCs) were investigated in BRNs/barosensitive neurons identified by conduction velocity (CV), capsaicin-conjugated with Iberiotoxin-sensitivity and fluorescent dye using intact nodose slice and brainstem slice in adult female rats. The expression of mRNA and targeted protein for NMDAR1 was also evaluated. Results: Ketamine time-dependently blocked afferent CV in Ah-types in nodose slice with significant changes in AP discharge. The concentration-dependent inhibition of ketamine on AP discharge profiles were also assessed and observed using isolated Ah-type BRNs with dramatic reduction in neuroexcitability. In brainstem slice, the 2nd-order capsaicin-resistant EPSCs were identified and ~50{\%} of them were blocked by ketamine concentration-dependently with IC50 estimated at 84.4 μM compared with the rest (708.2 μM). Interestingly, the peak, decay time constant, and area under curve of EPSCs were significantly enhanced by 100 nM iberiotoxin in ketamine-more sensitive myelinated NTS neurons (most likely Ah-types), rather than ketamine-less sensitive ones (A-types). Conclusions: These data have demonstrated, for the first time, that low-threshold and sex-specific myelinated Ah-type BRNs in nodose and Ah-type barosensitive neurons in NTS are more susceptible to ketamine and may play crucial roles in not only mean blood pressure regulation but also buffering dynamic changes in pressure, as well as the ketamine-mediated cardiovascular dysfunction through sexual-dimorphic baroreflex afferent pathway.",
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T1 - Ketamine-mediated afferent-specific presynaptic transmission blocks in low-threshold and sex-specific subpopulation of myelinated ah-type baroreceptor neurons of rats

AU - Wang, Lu Qi

AU - Liu, Sheng Zhi

AU - Wen, Xin

AU - Wu, Di

AU - Yin, Lei

AU - Fan, Yao

AU - Wang, Ye

AU - Chen, Wei Ran

AU - Chen, Pei

AU - Liu, Yang

AU - Lu, Xiao Long

AU - Sun, Hong Li

AU - Shou, Weinian

AU - Qiao, Guo Fen

AU - Li, Bai Yan

PY - 2015

Y1 - 2015

N2 - Background: Ketamine enhances autonomic activity, and unmyelinated C-type baroreceptor afferents are more susceptible to be blocked by ketamine than myelinated A-types. However, the presynaptic transmission block in low-threshold and sex-specific myelinated Ah-type baroreceptor neurons (BRNs) is not elucidated. Methods: Action potentials (APs) and excitatory post-synaptic currents (EPSCs) were investigated in BRNs/barosensitive neurons identified by conduction velocity (CV), capsaicin-conjugated with Iberiotoxin-sensitivity and fluorescent dye using intact nodose slice and brainstem slice in adult female rats. The expression of mRNA and targeted protein for NMDAR1 was also evaluated. Results: Ketamine time-dependently blocked afferent CV in Ah-types in nodose slice with significant changes in AP discharge. The concentration-dependent inhibition of ketamine on AP discharge profiles were also assessed and observed using isolated Ah-type BRNs with dramatic reduction in neuroexcitability. In brainstem slice, the 2nd-order capsaicin-resistant EPSCs were identified and ~50% of them were blocked by ketamine concentration-dependently with IC50 estimated at 84.4 μM compared with the rest (708.2 μM). Interestingly, the peak, decay time constant, and area under curve of EPSCs were significantly enhanced by 100 nM iberiotoxin in ketamine-more sensitive myelinated NTS neurons (most likely Ah-types), rather than ketamine-less sensitive ones (A-types). Conclusions: These data have demonstrated, for the first time, that low-threshold and sex-specific myelinated Ah-type BRNs in nodose and Ah-type barosensitive neurons in NTS are more susceptible to ketamine and may play crucial roles in not only mean blood pressure regulation but also buffering dynamic changes in pressure, as well as the ketamine-mediated cardiovascular dysfunction through sexual-dimorphic baroreflex afferent pathway.

AB - Background: Ketamine enhances autonomic activity, and unmyelinated C-type baroreceptor afferents are more susceptible to be blocked by ketamine than myelinated A-types. However, the presynaptic transmission block in low-threshold and sex-specific myelinated Ah-type baroreceptor neurons (BRNs) is not elucidated. Methods: Action potentials (APs) and excitatory post-synaptic currents (EPSCs) were investigated in BRNs/barosensitive neurons identified by conduction velocity (CV), capsaicin-conjugated with Iberiotoxin-sensitivity and fluorescent dye using intact nodose slice and brainstem slice in adult female rats. The expression of mRNA and targeted protein for NMDAR1 was also evaluated. Results: Ketamine time-dependently blocked afferent CV in Ah-types in nodose slice with significant changes in AP discharge. The concentration-dependent inhibition of ketamine on AP discharge profiles were also assessed and observed using isolated Ah-type BRNs with dramatic reduction in neuroexcitability. In brainstem slice, the 2nd-order capsaicin-resistant EPSCs were identified and ~50% of them were blocked by ketamine concentration-dependently with IC50 estimated at 84.4 μM compared with the rest (708.2 μM). Interestingly, the peak, decay time constant, and area under curve of EPSCs were significantly enhanced by 100 nM iberiotoxin in ketamine-more sensitive myelinated NTS neurons (most likely Ah-types), rather than ketamine-less sensitive ones (A-types). Conclusions: These data have demonstrated, for the first time, that low-threshold and sex-specific myelinated Ah-type BRNs in nodose and Ah-type barosensitive neurons in NTS are more susceptible to ketamine and may play crucial roles in not only mean blood pressure regulation but also buffering dynamic changes in pressure, as well as the ketamine-mediated cardiovascular dysfunction through sexual-dimorphic baroreflex afferent pathway.

KW - Baroreflex afferent pathway

KW - Ketamine (KET)

KW - Nodose ganglia (NG)

KW - Nucleus of the solitary tract (NTS)

KW - Pathology section

KW - Presynaptic neurotransmission

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