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KB-R7943, an inhibitor of the reverse Na+/Ca2+ exchanger, blocks N-methyl-D-aspartate receptor and inhibits mitochondrial complex I
Article first published online: 6 DEC 2010
DOI: 10.1111/j.1476-5381.2010.01054.x
© 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society
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How to Cite
Brustovetsky, T., Brittain, M. K., Sheets, P. L., Cummins, T. R., Pinelis, V. and Brustovetsky, N. (2011), KB-R7943, an inhibitor of the reverse Na+/Ca2+ exchanger, blocks N-methyl-D-aspartate receptor and inhibits mitochondrial complex I. British Journal of Pharmacology, 162: 255–270. doi: 10.1111/j.1476-5381.2010.01054.x
Publication History
- Issue published online: 6 DEC 2010
- Article first published online: 6 DEC 2010
- Accepted manuscript online: 30 SEP 2010 07:20AM EST
- Received , 5 April 2010 , Revised, 2 July 2010 , Accepted, 16 August 2010
References
- , , (2009). Guide to Receptors and Channels (GRAC), 4th edition. Br J Pharmacol 158 (Suppl. 2): S1–S254.
- , , (2003). Pharmacology of KB-R7943: a Na+-Ca2+ exchange inhibitor. Cardiovasc Drug Rev 21: 255–276.
- , , , , , et al. (2000). KB-R7943 inhibits store-operated Ca(2+) entry in cultured neurons and astrocytes. Biochem Biophys Res Commun 279: 354–357.
- , , , , , et al. (2007). Changes in calcium dynamics following the reversal of the sodium-calcium exchanger have a key role in AMPA receptor-mediated neurodegeneration via calpain activation in hippocampal neurons. Cell Death Differ 14: 1635–1646.
- , , , , , et al. (2005). Cleavage of the plasma membrane Na+/Ca2+ exchanger in excitotoxicity. Cell 120: 275–285.
- (1999). Mitochondrial transport of cations: channels, exchangers, and permeability transition. Physiol Rev 79: 1127–1155.
- , , , , , et al. (2006). The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J 273: 2077–2099.
- , (1999). Sodium/calcium exchange: its physiological implications. Physiol Rev 79: 763–854.
- (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254.
- , , , , (2000). Inhibition of different pathways influencing Na(+) homeostasis protects organotypic hippocampal slice cultures from hypoxic/hypoglycemic injury. Neuropharmacology 39: 1779–1787.
- , , , (2002). Calcium-induced cytochrome c release from CNS mitochondria is associated with the permeability transition and rupture of the outer membrane. J Neurochem 80: 207–218.
- , , (2009). Stimulation of glutamate receptors in cultured hippocampal neurons causes Ca2+-dependent mitochondrial contraction. Cell Calcium 46: 18–29.
- , , (2010). Calpain activation and Na(+)/Ca(2+) exchanger degradation occur downstream of calcium deregulation in hippocampal neurons exposed to excitotoxic glutamate. J Neurosci Res 88: 1317–1328.
- (1979). The calcium cycle of mitochondria. FEBS Lett 104: 1–5.
- , (1956). The respiratory chain and oxidative phosphorylation. Adv Enzymol Relat Subj Biochem 17: 65–134.
- , , , , , et al. (2007). AMPA-mediated excitotoxicity in oligodendrocytes: role for Na(+)-K(+)-Cl(-) co-transport and reversal of Na(+)/Ca(2+) exchanger. J Neurochem 102: 1783–1795.
- , , , , , et al. (1992). Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity. J Neurosci 12: 4427–4436.
- (1988). Glutamate neurotoxicity and diseases of the nervous system. Neuron 1: 623–634.
- , , (1989). Ketamine and MK-801 prevent degeneration of thalamic neurons induced by focal cortical seizures. Exp Neurol 105: 272–279.
- , (1999). Comparison of Na+-Ca2+ exchange current elicited from isolated rabbit ventricular myocytes by voltage ramp and step protocols. Pflugers Arch 437: 944–954.
- , (2002). In depolarized and glucose-deprived neurons, Na+ influx reverses plasmalemmal K+-dependent and K+-independent Na+/Ca2+ exchangers and contributes to NMDA excitotoxicity. J Neurochem 83: 1321–1328.
- , , (2002). Instrumental role of Na+ in NMDA excitotoxicity in glucose-deprived and depolarized cerebellar granule cells. J Neurochem 81: 379–389.
- , , (2007). Contribution of Na(+)/Ca(2+) exchange to excessive Ca(2+) loading in dendrites and somata of CA1 neurons in acute slice. Hippocampus 17: 1049–1059.
- (1993). Intracellular calcium levels during the period of delayed excitotoxicity. J Neuroscience 13: 623–631.
- , , (1995). An obligate role for oxygen in the early stages of glutamate-induced, delayed neuronal death. J Neurosci 15: 7071–7078.
- , (1992). Mitochondrial function in type I cells isolated from rabbit arterial chemoreceptors. J Physiol 450: 13–31.
- , , (2006). Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders. Pharmacol Rev 58: 591–620.
- , , , (1998). Reverse Na+/Ca2+ exchange contributes to glutamate-induced intracellular Ca2+ concentration increases in cultured rat forebrain neurons. Mol Pharmacol 53: 742–749.
- , (2006). YM-244769, a novel Na+/Ca2+ exchange inhibitor that preferentially inhibits NCX3, efficiently protects against hypoxia/reoxygenation-induced SH-SY5Y neuronal cell damage. Mol Pharmacol 70: 2075–2083.
- , , (1996). A novel isothiourea derivative selectively inhibits the reverse mode of Na+/Ca2+ exchange in cells expressing NCX1. J Biol Chem 271: 22391–22397.
- (2007). NCX and NCKX operation in ischemic neurons. Ann N Y Acad Sci 1099: 383–395.
- , , , (1994). Glutamate impairs neuronal calcium extrusion while reducing sodium gradient. Neuron 12: 295–300.
- (2007). The Na+/Ca2+ exchange inhibitor KB-R7943 potently blocks TRPC channels. Biochem Biophys Res Commun 361: 230–236.
- , , (1993). Principles of Biochemistry. Worth Publishers: New York.
- , , (2000). Important role of reverse Na(+)-Ca(2+) exchange in spinal cord white matter injury at physiological temperature. J Neurophysiol 84: 1116–1119.
- , , , (2008). Oligomeric BAX induces mitochondrial permeability transition and complete cytochrome c release without oxidative stress. Biochim Biophys Acta 1777: 1409–1421.
- , , (2009). Role of cyclophilin d-dependent mitochondrial permeability transition in glutamate-induced calcium deregulation and excitotoxic neuronal death. Exp Neurol 218: 171–182.
- , , , , , et al. (2007). Increased tolerance to ischemic neuronal damage by knockdown of Na+-Ca2+ exchanger isoform 1. Ann N Y Acad Sci 1099: 292–305.
- , , (2003). Brain edema induced by in vitro ischemia: causal factors and neuroprotection. J Neurochem 85: 1402–1411.
- , , , (1989). Delayed increase of Ca2+ influx elicited by glutamate: role in neuronal death. Mol Pharmacol 36: 106–112.
- , , , , , et al. (2001). SEA0400, a novel and selective inhibitor of the Na+-Ca2+ exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models. J Pharmacol Exp Ther 298: 249–256.
- , , (1989). A role for Na+-dependent Ca2+ extrusion in protection against neuronal excitotoxicity. FASEB J 3: 2519–2526.
- , (1987). Permeation and block of N-methyl-D-aspartic acid receptor channels by divalent cations in mouse cultured central neurones. J Physiol 394: 501–527.
- , , , , (2006). Quantitative fluorescence measurement of cardiac Na+/Ca2+ exchanger inhibition by kinetic analysis in stably transfected HEK293 cells. J Pharmacol Sci 101: 356–360.
- , , (1969). The inhibition by 2,4-dinitrophenol of the removal of oxaloacetate formed by the oxidation of succinate by rat-liver and -heart mitochondria. Biochim Biophys Acta 180: 45–55.
- , , , , (2005). Protection of ischemic rat spinal cord white matter: dual action of KB-R7943 on Na+/Ca2+ exchange and L-type Ca2+ channels. Neuropharmacology 48: 566–575.
- , , , , , (2004). Excitotoxic calcium overload in a subpopulation of mitochondria triggers delayed death in hippocampal neurons. J Neurosci 24: 5611–5622.
- , , , , , et al. (2007). Functional expression of the Na+/Ca2+ exchanger in the embryonic mouse heart. J Mol Cell Cardiol 42: 121–132.
- , , , , , et al. (2007). The plasma membrane Na+/Ca2+ exchange inhibitor KB-R7943 is also a potent inhibitor of the mitochondrial Ca2+ uniporter. Br J Pharmacol 151: 647–654.
- , , , (1999). The novel Na+/Ca2+ exchange inhibitor KB-R7943 protects CA1 neurons in rat hippocampal slices against hypoxic/hypoglycemic injury. Neuropharmacology 38: 319–321.
- , , (2007). Lithium desensitizes brain mitochondria to calcium, antagonizes permeability transition, and diminishes cytochrome C release. J Biol Chem 282: 18057–18068.
- , , , , (2006). Na(+)/Ca(2+) exchanger expression and function in a rabbit model of myocardial infarction. J Cardiovasc Electrophysiol 17 (Suppl. 1): S57–S63. Direct Link:
- , (1999). Blockade of NMDA channels in acutely isolated rat hippocampal neurons by the Na+/Ca2+ exchange inhibitor KB-R7943. Neuropharmacology 38: 1235–1242.
- , , , , (2010). Neuroprotective effect of KB-R7943 against glutamate excitotoxicity is related to mild mitochondrial depolarization. Neurochem Res 35: 323–335.
- , , , , (1998). Glutamate-induced neuron death requires mitochondrial calcium uptake. Nat Neurosci 1: 366–373.
- , (2000). Inhibitory effect of amiodarone on Na(+)/Ca(2+) exchange current in guinea-pig cardiac myocytes. Br J Pharmacol 131: 80–84.
- , , (2006). Topics on the Na+/Ca2+ exchanger: pharmacological characterization of Na+/Ca2+ exchanger inhibitors. J Pharmacol Sci 102: 7–16.
- , , , (2008). Reverse mode Na+/Ca2+ exchangers trigger the release of Ca2+ from intracellular Ca2+ stores in cultured rat embryonic cortical neurons. Brain Res 1201: 41–51.