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Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but a structural understanding of anesthetic action on pLGICs remains elusive. GLIC, a prokaryotic pLGIC, can be inhibited by anesthetics, including ketamine. The ketamine concentration leading to half-maximal inhibition of GLIC (58 μM) is comparable to that on neuronal(More)
Neurotransmitter transporters are membrane proteins that serve as key regulators of extracellular neurotransmitter concentrations and have been long viewed as important targets for drug development by the pharmaceutical industry. Although many cellular signaling systems are known to modulate transport activity, much less is known about how transporters(More)
Excitatory amino acid transporters or EAATs are the major transport mechanism for extracellular glutamate in the nervous system. This family of five carriers not only displays an impressive ability to regulate ambient extracellular glu concentrations but also regulate the temporal and spatial profile of glu after vesicular release. This dynamic form of(More)
Excitatory amino acid transporters (EAATs) limit glutamatergic signaling and maintain extracellular glutamate concentrations below neurotoxic levels. Of the five known EAAT isoforms (EAATs 1-5), only the neuronal isoform, EAAT3 (EAAC1), can efficiently transport the uncharged amino acid L-cysteine. EAAT3-mediated cysteine transport has been proposed to be a(More)
In the mammalian central nervous system, excitatory amino acid transporters (EAATs) are responsible for the clearance of glutamate after synaptic release. This energetically demanding activity is crucial for precise neuronal communication and for maintaining extracellular glutamate concentrations below neurotoxic levels. In addition to their ability to(More)
Christopher B. Divito,1 Kathy Steece-Collier,3 Daniel T. Case,1 Sean-Paul G. Williams,1 Jennifer A. Stancati,3 Lianteng Zhi,4 Maria E. Rubio,2 X Caryl E. Sortwell,3 Timothy J. Collier,3 David Sulzer,5 Robert H. Edwards,6 Hui Zhang,4 and Rebecca P. Seal1,2 1Department of Neurobiology and 2Department of Otolaryngology, University of Pittsburgh School of(More)
UNLABELLED The striatum is essential for many aspects of mammalian behavior, including motivation and movement, and is dysfunctional in motor disorders such as Parkinson's disease. The vesicular glutamate transporter 3 (VGLUT3) is expressed by striatal cholinergic interneurons (CINs) and is thus well positioned to regulate dopamine (DA) signaling and(More)
Formetanate hydrochloride is a bifunctional pesticide with remarkable solubility, high toxicity, and potential mobility in aqueous environments. The relative stability of the formamidine and carbamate groups in this compound can be used to predict the identity of its degradation products in water. The reported NMR and UV-vis spectroscopic studies revealed(More)
Excitatory amino acid transporters (EAATs) are secondary active transporters of L-glutamate and L- or D-aspartate. These carriers also mediate a thermodynamically uncoupled anion conductance that is gated by Na+ and substrate binding. The activation of the anion channel by binding of Na+ alone, however, has only been demonstrated for mammalian EAAC1 (EAAT3)(More)
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