PMID- 29034474
OWN - NLM
STAT- MEDLINE
DCOM- 20180718
LR  - 20191128
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Print)
IS  - 0022-3751 (Linking)
VI  - 595
IP  - 24
DP  - 2017 Dec 15
TI  - Altered NMDA receptor-evoked intracellular Ca(2+) dynamics in magnocellular 
      neurosecretory neurons of hypertensive rats.
PG  - 7399-7411
LID - 10.1113/JP275169 [doi]
AB  - KEY POINTS: NMDA receptor (NMDAR)-mediated Ca(2+) signalling plays a critical 
      role in modulating hypothalamic neurosecretory function. However, whether an 
      altered NMDAR-evoked changes in Ca(2+) (NMDAR-DeltaCa(2+) ) signalling in 
      magnocellular neurosecretory cells (MNCs) may contribute to neurohumoral 
      activation during disease states is unknown. We show that activation of NMDARs 
      evoked similar inward currents in MNCs of sham and renovascular hypertensive 
      (RVH) rats. Despite this, a prolonged and larger NMDAR-DeltaCa(2+) response was 
      observed in the latter. The exacerbated NMDAR-DeltaCa(2+) responses in MNCs of RVH 
      rats affected both somatic and dendritic compartments. Inhibition of the 
      endoplasmic reticulum sarcoendoplasmic reticulum calcium trasport ATPase (SERCA) 
      pump prolonged NMDAR-DeltaCa(2+) responses in sham rats, but not in RVH rats. Our 
      study supports an altered spatiotemporal dynamic of NMDAR-DeltaCa(2+) signalling in 
      MNCs from RVH rats, partly due to blunted endoplasmic reticulum Ca(2+) buffering 
      capacity. ABSTRACT: A growing body of evidence supports an elevated NMDA receptor 
      (NMDAR)-mediated glutamate excitatory function in the supraoptic nucleus and 
      paraventricular nucleus of hypertensive rats that contributes to neurohumoral 
      activation in this disease. However, the precise mechanisms underlying altered 
      NMDAR signalling in hypertension remain to be elucidated. In this study, we 
      performed simultaneous electrophysiology and fast confocal Ca(2+) imaging to 
      determine whether altered NMDAR-mediated changes in intracellular Ca(2+) levels 
      (NMDAR-DeltaCa(2+) ) occurred in hypothalamic magnocellular neurosecretory cells 
      (MNCs) in renovascular hypertensive (RVH) rats. We found that despite evoking a 
      similar excitatory inward current, activation of NMDARs resulted in a larger and 
      prolonged DeltaCa(2+) in MNCs from RVH rats. Changes in NMDAR-DeltaCa(2+) dynamics were 
      observed both in somatic and dendritic compartments. Inhibition of the 
      sarcoendoplasmic reticulum calcium trasport ATPase (SERCA) pump activity with 
      thapsigargin prolonged NMDAR-DeltaCa(2+) responses in MNCs of sham rats, but this 
      effect was occluded in RVH rats, thus equalizing the magnitude and time course of 
      the NMDA-DeltaCa(2+) responses between the two experimental groups. Taken together, 
      our results support (1) an exacerbated NMDAR-DeltaCa(2+) response in somatodendritic 
      compartments of MNCs of RVH rats, and (2) that a blunted ER Ca(2+) buffering 
      capacity contributes to the altered NMDAR-DeltaCa(2+) dynamics in this condition. 
      Thus, altered spatiotemporal dynamics of the NMDAR-DeltaCa(2+) response stands as an 
      underlying mechanism contributing to neurohumoral activation in neurogenic 
      hypertension.
CI  - (c) 2017 The Authors. The Journal of Physiology (c) 2017 The Physiological Society.
FAU - Zhang, Meng
AU  - Zhang M
AD  - Department of Physiology, Medical College of Georgia, Augusta University, 1120 
      15th Street, Augusta, GA 30912, USA.
FAU - Stern, Javier E
AU  - Stern JE
AUID- ORCID: 0000-0002-9310-0486
AD  - Department of Physiology, Medical College of Georgia, Augusta University, 1120 
      15th Street, Augusta, GA 30912, USA.
LA  - eng
GR  - R01 HL112225/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20171115
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
SB  - IM
MH  - Animals
MH  - *Calcium Signaling
MH  - Hypertension/*metabolism
MH  - Male
MH  - Neurons/*metabolism
MH  - Paraventricular Hypothalamic Nucleus/cytology/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism
MH  - Supraoptic Nucleus/cytology/*metabolism
PMC - PMC5730840
OTO - NOTNLM
OT  - NMDA
OT  - endoplasmic reticulum
OT  - glutamate
OT  - hypothalamus
EDAT- 2017/10/17 06:00
MHDA- 2018/07/19 06:00
PMCR- 2018/12/15
CRDT- 2017/10/17 06:00
PHST- 2017/08/24 00:00 [received]
PHST- 2017/10/03 00:00 [accepted]
PHST- 2017/10/17 06:00 [pubmed]
PHST- 2018/07/19 06:00 [medline]
PHST- 2017/10/17 06:00 [entrez]
PHST- 2018/12/15 00:00 [pmc-release]
AID - TJP12674 [pii]
AID - 10.1113/JP275169 [doi]
PST - ppublish
SO  - J Physiol. 2017 Dec 15;595(24):7399-7411. doi: 10.1113/JP275169. Epub 2017 Nov 
      15.