Comparative impact of voltage-gated calcium channels and NMDA receptors on mitochondria-mediated neuronal injury.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Ruslan I StanikaNatalia B Pivovarova

Abstract

Glutamate excitotoxicity, a major component of many neurodegenerative disorders, is characterized by excessive calcium influx selectively through NMDARs. However, there is a substantial uncertainty concerning why other known routes of significant calcium entry, in particular, VGCCs, are not similarly toxic. Here, we report that in the majority of neurons in rat hippocampal and cortical cultures, maximal L-type VGCC activation induces much lower calcium loading than toxic NMDAR activation. Consequently, few depolarization-activated neurons exhibit calcium deregulation and cell death. Activation of alternative routes of calcium entry induced neuronal death in proportion to the degree of calcium loading. In a small subset of neurons, depolarization evoked stronger calcium elevations, approaching those induced by toxic NMDA. These neurons were characterized by elevated expression of VGCCs and enhanced voltage-gated calcium currents, mitochondrial dysfunction and cell death. Preventing VGCC-dependent mitochondrial calcium loading resulted in stronger cytoplasmic calcium elevations, whereas inhibiting mitochondrial calcium clearance accelerated mitochondrial depolarization. Both observations further implicate mitochondrial dysfunctio...Continue Reading

References

Apr 10, 1999·Nature Neuroscience·A K StoutI J Reynolds
Jun 18, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Natalia B PivovarovaS Brian Andrews
Jul 15, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jeremy D MarksJanice Wang
May 16, 2006·Current Opinion in Neurobiology·Shin Kwak, John H Weiss
May 13, 2008·Biochimica Et Biophysica Acta·Andrey Y Abramov, Michael R Duchen
Jul 12, 2008·Methods in Cell Biology·E Fernandez-Segura, Alice Warley
Oct 17, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Francesc X SorianoGiles E Hardingham
Dec 17, 2008·Annals of the New York Academy of Sciences·David G Nicholls
Dec 19, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Valentina Di BiaseBernhard E Flucher
Feb 24, 2009·Trends in Molecular Medicine·Ilya Bezprozvanny
Mar 21, 2009·Biochimica Et Biophysica Acta·David G Nicholls
Mar 24, 2009·The Mount Sinai Journal of Medicine, New York·Mark W Greve, Brian J Zink
Jun 2, 2009·Proceedings of the National Academy of Sciences of the United States of America·Ruslan I StanikaS Brian Andrews
Feb 20, 2010·Cell Calcium·Kinga Szydlowska, Michael Tymianski
Jul 28, 2010·The FEBS Journal·Natalia B Pivovarova, S Brian Andrews
Sep 16, 2010·Nature Reviews. Neuroscience·Giles E Hardingham, Hilmar Bading

❮ Previous
Next ❯

Citations

Dec 18, 2013·Brain Research Bulletin·J Nicholas CochranErik D Roberson
Jan 11, 2013·Cell Death & Disease·A VaarmannA Y Abramov
Apr 30, 2014·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Sangwoo RyuIn-Young Choi
Sep 14, 2014·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Maja Jazvinšćak JembrekNada Oršolić
Jan 1, 2014·Antioxidants·Rachel ShirleyLorraine M Work
Oct 17, 2013·Journal of Neurochemistry·Natalia B PivovarovaS Brian Andrews
Apr 5, 2014·Neuron·Brett A Simms, Gerald W Zamponi
Dec 3, 2014·Neurobiology of Aging·Ildete Luísa FerreiraA Cristina Rego
Mar 19, 2014·Antioxidants & Redox Signaling·Angela M Brennan-MinnellaRaymond A Swanson
Feb 24, 2018·Journal of Neurochemistry·Jens IngwersenTim Prozorovski
Oct 1, 2013·Reviews in the Neurosciences·Sukant Khurana, Wen-Ke Li
Oct 6, 2020·Frontiers in Neuroscience·Jiejie Wang, Raymond A Swanson
Nov 6, 2018·International Journal of Molecular Sciences·Yilin MaoMelinda Fitzgerald
Apr 3, 2019·Nature Chemical Biology·Younghee OhMichael Z Lin
Dec 31, 2020·International Journal of Molecular Sciences·Erzsébet KövesdiIstván M Abrahám
Mar 31, 2021·Proceedings of the National Academy of Sciences of the United States of America·Clemens L SchöpfGerald J Obermair
May 15, 2021·Orphanet Journal of Rare Diseases·Miriam KessiFei Yin

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.