4 years ago

Altered NMDA receptor-evoked intracellular Ca(2+) dynamics in magnocellular neurosecretory neurons of hypertensive rats.

Javier E Stern, Meng Zhang
A growing body of evidence supports an elevated NMDA receptor-mediated glutamate excitatory function in the SON and PVN of hypertensive rats that contributes to neurohumoral activation in this disease. Still, the precise mechanisms underlying altered NMDAR signalling in hypertension remains to be elucidated. In this study, we performed simultaneous electrophysiology and fast confocal Ca(2+) imaging to determine whether an altered NMDAR-mediated changes in intracellular Ca(2+) levels (NMDAR-ΔCa(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 ΔCa(2+) in MNCs from RVH rats. Changes in NMDAR-ΔCa(2+) dynamics were observed both in somatic and dendritic compartments. Inhibition of the ER SERCA pump activity with thapsigargin prolonged NMDAR-ΔCa(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-ΔCa(2) responses between the two experimental groups. Taken together, our results support (1) an exacerbated NMDAR-ΔCa(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-ΔCa(2+) dynamics in this condition. Thus, an altered spatiotemporal dynamics of NMDAR-ΔCa(2+) response stands as an underlying mechanisms contributing to neurohumoral activation in neurogenic hypertension. This article is protected by copyright. All rights reserved.

Publisher URL: http://doi.org/10.1113/JP275169

DOI: 10.1113/JP275169

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.