PMID- 28637815
OWN - NLM
STAT- MEDLINE
DCOM- 20180503
LR  - 20181202
IS  - 1522-1598 (Electronic)
IS  - 0022-3077 (Print)
IS  - 0022-3077 (Linking)
VI  - 118
IP  - 3
DP  - 2017 Sep 1
TI  - The proinflammatory cytokine tumor necrosis factor-alpha excites subfornical organ 
      neurons.
PG  - 1532-1541
LID - 10.1152/jn.00238.2017 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine implicated in 
      cardiovascular and autonomic regulation via actions in the central nervous 
      system. TNF-alpha(-/-) mice do not develop angiotensin II (ANG II)-induced 
      hypertension, and administration of TNF-alpha into the bloodstream of rats increases 
      blood pressure and sympathetic tone. Recent studies have shown that lesion of the 
      subfornical organ (SFO) attenuates the hypertensive and autonomic effects of 
      TNF-alpha, while direct administration of TNF-alpha into the SFO increases blood 
      pressure, suggesting the SFO to be a key site for the actions of TNF-alpha. 
      Therefore, we used patch-clamp techniques to examine both acute and long-term 
      effects of TNF-alpha on the excitability of Sprague-Dawley rat SFO neurons. It was 
      observed that acute bath application of TNF-alpha depolarized SFO neurons and 
      subsequently increased action potential firing rate. Furthermore, the magnitude 
      of depolarization and the proportion of depolarized SFO neurons were 
      concentration dependent. Interestingly, following 24-h incubation with TNF-alpha, the 
      basal firing rate of the SFO neurons was increased and the rheobase was 
      decreased, suggesting that TNF-alpha elevates SFO neuron excitability. This effect 
      was likely mediated by the transient sodium current, as TNF-alpha increased the 
      magnitude of the current and lowered its threshold of activation. In contrast, 
      TNF-alpha did not appear to modulate either the delayed rectifier potassium current 
      or the transient potassium current. These data suggest that acute and long-term 
      TNF-alpha exposure elevates SFO neuron activity, providing a basis for TNF-alpha 
      hypertensive and sympathetic effects.NEW & NOTEWORTHY Considerable recent 
      evidence has suggested important links between inflammation and the pathological 
      mechanisms underlying hypertension. The present study describes cellular 
      mechanisms through which acute and long-term exposure of tumor necrosis factor-alpha 
      (TNF-alpha) influences the activity of subfornical organ neurons by modulating the 
      voltage-gated transient Na(+) current. This provides critical new information 
      regarding the specific pathological mechanisms through which inflammation and 
      TNF-alpha in particular may result in the development of hypertension.
CI  - Copyright (c) 2017 the American Physiological Society.
FAU - Simpson, Nick J
AU  - Simpson NJ
AD  - Department of Biomedical and Molecular Sciences and Centre for Neuroscience 
      Studies, Queen's University, Kingston, Ontario, Canada.
FAU - Ferguson, Alastair V
AU  - Ferguson AV
AUID- ORCID: 0000-0003-1261-0036
AD  - Department of Biomedical and Molecular Sciences and Centre for Neuroscience 
      Studies, Queen's University, Kingston, Ontario, Canada avf@queensu.ca.
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170621
PL  - United States
TA  - J Neurophysiol
JT  - Journal of neurophysiology
JID - 0375404
RN  - 0 (Potassium Channels)
RN  - 0 (Sodium Channels)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - *Action Potentials
MH  - Animals
MH  - Cells, Cultured
MH  - Male
MH  - Neurons/*drug effects/metabolism/physiology
MH  - Potassium Channels/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sodium Channels/metabolism
MH  - Subfornical Organ/cytology/*drug effects/physiology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
PMC - PMC5596133
OTO - NOTNLM
OT  - angiotensin II
OT  - inflammation
OT  - patch-clamp electrophysiology
OT  - subfornical organ
OT  - tumor necrosis factor-alpha
EDAT- 2017/06/24 06:00
MHDA- 2018/05/04 06:00
PMCR- 2018/09/01
CRDT- 2017/06/23 06:00
PHST- 2017/03/29 00:00 [received]
PHST- 2017/06/15 00:00 [revised]
PHST- 2017/06/15 00:00 [accepted]
PHST- 2017/06/24 06:00 [pubmed]
PHST- 2018/05/04 06:00 [medline]
PHST- 2017/06/23 06:00 [entrez]
PHST- 2018/09/01 00:00 [pmc-release]
AID - jn.00238.2017 [pii]
AID - JN-00238-2017 [pii]
AID - 10.1152/jn.00238.2017 [doi]
PST - ppublish
SO  - J Neurophysiol. 2017 Sep 1;118(3):1532-1541. doi: 10.1152/jn.00238.2017. Epub 
      2017 Jun 21.