title: Ketamine-mediated afferent-specific presynaptic transmission blocks in low-threshold and sex-specific subpopulation of myelinated Ah-type baroreceptor neurons of rats.
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.
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.|Key Laboratory of Cardiovascular Medicine Research of Ministry of Education, Harbin Medical University, Harbin, China.
authors.forename: Lu-Qi
authors.initials: LQ
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.
authors.forename: Sheng-Zhi
authors.initials: SZ
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wen
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research of Ministry of Education, Harbin Medical University, Harbin, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research of Ministry of Education, Harbin Medical University, Harbin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Pharmacology, Daqing Campus of Harbin Medical University, Daqing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.
authors.forename: Wei-Ran
authors.initials: WR
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research of Ministry of Education, Harbin Medical University, Harbin, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, Daqing Campus of Harbin Medical University, Daqing, China.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Sun
authors.affiliation: Riley Heart Research Center, Division of Pediatric Cardiology, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Weinian
authors.initials: W
authors.lastname: Shou
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.|Key Laboratory of Cardiovascular Medicine Research of Ministry of Education, Harbin Medical University, Harbin, China.
authors.forename: Guo-Fen
authors.initials: GF
authors.lastname: Qiao
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.
authors.forename: Bai-Yan
authors.initials: BY
authors.lastname: Li
mesh_terms: D000200:Action Potentials; D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism; D000778:Anesthetics, Dissociative / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D007649:Ketamine / Q000633:toxicity*; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000378:metabolism; D009431:Neural Conduction / Q000187:drug effects; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011311:Pressoreceptors / Q000187:drug effects* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D012737:Sex Factors; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000778:Anesthetics, Dissociative; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Pathology Section; baroreflex afferent pathway; ketamine (Ket); nodose ganglia (NG); nucleus of the solitary tract (NTS); presynaptic neurotransmission