Title

Nmda Receptor Activation Contributes To A Portion Of The Decreased Mitochondrial Membrane Potential And Elevated Intracellular Free Calcium In Strain-Injured Neurons

Keywords

APV; Calcium; Glutamate; Mitochondria; MK-801; Traumatic brain injury

Abstract

In our previous studies, we have shown that in vitro biaxial strain (stretch) injury of neurons in neuronal plus glial cultures increases intracellular free calcium ([Ca2+]i) and decreases mitochondrial membrane potential (ΔΨm). The goal of this study was to determine whether strain injury, without the addition of exogenous agents, causes glutamate release, and whether NMDA receptor antagonists affect the post-strain injury rise in [Ca2+]i and decrease in ΔΨm. [Ca2+]i and ΔΨm were measured using the fluorescent indicators fura-2 AM and rhodamine-1,2,3 (rh123). Strain injury of neuronal plus glial cultures caused an immediate 100-200 nM elevation in neuronal [Ca2+]i and a decline in neuronal ΔΨm by 15 min post-injury. Pretreatment with the NMDA receptor antagonist MK-801 (10 μM) attenuated the [Ca2+]i elevation after mild, but not moderate and severe injury. MK-801 pretreatment reduced the decline in ΔΨm after mild and moderate, but not after severe injury. The NMDA receptor antagonist D-2-amino-5-phosphonopentanoic acid (APV; 100 μM) had effects similar to MK-801. Simultaneous measurement of [Ca2+]i and ΔΨm demonstrated a significant correlation and a temporal relationship between [Ca2+]i elevation and depression of ΔΨm. We conclude that NMDA receptor stimulation contributes to some of the changes in [Ca2+]i and ΔΨm after less severe strain injury. However, after more pronounced injury other mechanisms appear to be more involved.

Publication Date

12-1-2002

Publication Title

Journal of Neurotrauma

Volume

19

Issue

12

Number of Pages

1619-1629

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1089/089771502762300274

Socpus ID

0036931846 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/0036931846

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