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Title: Dinuclear nitrido-bridged osmium complexes inhibit the mitochondrial calcium uniporter and protect cortical neurons against lethal oxygen–glucose deprivation

We have investigated the biological properties of the osmium analogue of a potent ruthenium-based mitochondrial calcium uniporter inhibitor and have found it to possess distinct properties.

 
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Award ID(s):
1750295
NSF-PAR ID:
10467007
Author(s) / Creator(s):
; ; ; ;
Publisher / Repository:
Royal Society of Chemistry
Date Published:
Journal Name:
RSC Chemical Biology
Volume:
4
Issue:
1
ISSN:
2633-0679
Page Range / eLocation ID:
84 to 93
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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    Research into perovskite nanocrystals (PNCs) has uncovered interesting properties compared to their bulk counterparts, including tunable optical properties due to size‐dependent quantum confinement effect (QCE). More recently, smaller PNCs with even stronger QCE have been discovered, such as perovskite magic sized clusters (PMSCs) and ligand passivated PbX2metal halide molecular clusters (MHMCs) analogous to perovskites.

    Objective

    This review aims to present recent data comparing and contrasting the optical and structural properties of PQDs, PMSCs, and MHMCs, where CsPbBr3PQDs have first excitonic absorption around 520 nm, the corresponding PMSCS have absorption around 420 nm, and ligand passivated MHMCs absorb around 400 nm.

    Results

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    Recent study of novel clusters has led to better understanding of their properties. The sharper optical bands of clusters indicate relatively narrow or single size distribution, which, in conjunction with their blue absorption and emission, makes them potentially attractive for applications in fields such as blue single photon emission.

     
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    Triheteromeric NMDA receptors contain two GluN1 and two distinct GluN2 subunits and mediate excitatory neurotransmission in the CNS.

    Triheteromeric GluN1/2B/2D receptors have functional properties intermediate to those of diheteromeric GluN1/2B and GluN1/2D receptors.

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    Abstract

    Triheteromeric NMDA‐type glutamate receptors that contain two GluN1 and two different GluN2 subunits contribute to excitatory neurotransmission in the adult CNS. In the present study, we report properties of the triheteromeric GluN1/2B/2D NMDA receptor subtype that is expressed in distinct neuronal populations throughout the CNS. We show that neither GluN2B, nor GluN2D dominate the functional properties of GluN1/2B/2D receptors because agonist potencies, open probability and the glutamate deactivation time course of GluN1/2B/2D receptors are intermediate to those of diheteromeric GluN1/2B and GluN1/2D receptors. Furthermore, channel blockade of GluN1/2B/2D by extracellular Mg2+is intermediate compared to GluN1/2B and GluN1/2D, although GluN1/2B/2D is more sensitive to blockade by ketamine and memantine compared to GluN1/2B in the presence of physiological Mg2+. Subunit‐selective allosteric modulators have distinct activity at GluN1/2B/2D receptors, including GluN2B‐selective antagonists, ifenprodil, EVT‐101 and CP‐101‐606, which inhibit with similar potencies but with different efficacies at GluN1/2B/2D (∼65% inhibition) compared to GluN1/2B (∼95% inhibition). Furthermore, the GluN2B‐selective positive allosteric modulator spermine enhances responses from GluN1/2B/2D but not GluN1/2A/2B receptors. We show that these key features of allosteric modulation of recombinant GluN1/2B/2D receptors are also observed for NMDA receptors in hippocampal interneurons but not CA1 pyramidal cells, which is consistent with the expression of GluN1/2B/2D receptors in interneurons and GluN1/2A/2B receptors in pyramidal cells. Altogether, we uncover previously unknown functional and pharmacological properties of triheteromeric GluN1/2B/2D receptors that can facilitate advances in our understanding of their physiological roles in neural circuit function and therapeutic drug actions.

     
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