Abstract:
:The clinical efficacy of local anesthetic and antiarrhythmic drugs is due to their voltage- and frequency-dependent block of Na+ channels. Quaternary local anesthetic analogs such as QX-314, which are permanently charged and membrane-impermeant, effectively block cardiac Na+ channels when applied from either side of the membrane but block neuronal Na+ channels only from the intracellular side. This difference in extracellular access to QX-314 is retained when rat brain rIIA Na+ channel alpha subunits and rat heart rH1 Na+ channel alpha subunits are expressed transiently in tsA-201 cells. Amino acid residues in transmembrane segment S6 of homologous domain IV (IVS6) of Na+ channel alpha subunits have important effects on block by local anesthetic drugs. Although five amino acid residues in IVS6 differ between brain rIIA and cardiac rH1, exchange of these amino acid residues by site-directed mutagenesis showed that only conversion of Thr-1755 in rH1 to Val as in rIIA was sufficient to reduce the rate and extent of block by extracellular QX-314 and slow the escape of drug from closed channels after use-dependent block. Tetrodotoxin also reduced the rate of block by extracellular QX-314 and slowed escape of bound QX-314 via the extracellular pathway in rH1, indicating that QX-314 must move through the pore to escape. QX-314 binding was inhibited by mutation of Phe-1762 in the local anesthetic receptor site of rH1 to Ala whether the drug was applied extracellularly or intracellularly. Thus, QX-314 binds to a single site in the rH1 Na+ channel alpha subunit that contains Phe-1762, whether it is applied from the extracellular or intracellular side of the membrane. Access to that site from the extracellular side of the pore is determined by the amino acid at position 1755 in the rH1 cardiac Na+ channel.
journal_name
Proc Natl Acad Sci U S Aauthors
Qu Y,Rogers J,Tanada T,Scheuer T,Catterall WAdoi
10.1073/pnas.92.25.11839subject
Has Abstractpub_date
1995-12-05 00:00:00pages
11839-43issue
25eissn
0027-8424issn
1091-6490journal_volume
92pub_type
杂志文章abstract::Although sunlight provides the energy necessary for plants to survive and grow, light can also damage reaction centers of photosystem II (PSII) and reduce photochemical efficiency. To prevent damage, plants possess photoprotective mechanisms that dissipate excess excitation. A subset of these mechanisms is collectivel...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1704373114
更新日期:2017-08-15 00:00:00
abstract::A predictive coarse-grained protein force field [associative memory, water-mediated, structure, and energy model for molecular dynamics (AWSEM)-MD] is used to study the energy landscapes and relative stabilities of amyloid-β protein (1-40) in the monomer and all of its oligomeric forms up to an octamer. We find that a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1612362113
更新日期:2016-10-18 00:00:00
abstract::The kidney develops through reciprocal interactions between two precursor tissues: the metanephric mesenchyme and the ureteric bud. We previously demonstrated that the zinc finger protein Sall1 is essential for ureteric bud attraction toward the mesenchyme. Here, we show that Kif26b, a kinesin family gene, is a downst...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0913748107
更新日期:2010-05-18 00:00:00
abstract::The physiological significance of multiple G-protein-coupled receptor subtypes, such as the beta-adrenergic receptors (beta ARs), remains obscure, since in many cases several subtypes activate the same effector and utilize the same physiological agonists. We inspected the deduced amino acid sequences of the beta AR su...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.8.3665
更新日期:1993-04-15 00:00:00
abstract::Host-encoded factors play an important role in virus multiplication, acting in concert with virus-encoded factors. However, information regarding the host factors involved in this process is limited. Here we report the map-based cloning of an Arabidopsis thaliana gene, TOM1, which is necessary for the efficient multip...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.170295097
更新日期:2000-08-29 00:00:00
abstract::Eusociality is a major evolutionary innovation involving alterations in life history, morphology, and behavior. Advanced eusocial insects, such as ants, termites, and corbiculate bees, cannot provide insights into the earliest stages of eusocial evolution because eusociality in these taxa evolved long ago (in the Cret...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.012387999
更新日期:2002-01-08 00:00:00
abstract::Telomerase activity was identified in extracts from several different mouse cell lines. Addition of telomeric TTAGGG repeats was specific to telomeric oligonucleotide primers and sensitive to pretreatment with RNase A. In contrast to the hundreds of repeats synthesized by the human and Tetrahymena telomerase enzymes i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.4.1493
更新日期:1993-02-15 00:00:00
abstract::Bacillus anthracis, the etiologic agent of anthrax, avoids immune surveillance and commandeers host macrophages as a vehicle for lymphatic spreading. Here, we show that B. anthracis edema toxin (ET), via its adenylyl cyclase activity, dramatically increases the motility of infected macrophages and the expression of va...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0800105105
更新日期:2008-04-22 00:00:00
abstract::The explosive growth in citizen science combined with a recalcitrance on the part of mainstream science to fully embrace this data collection technique demands a rigorous examination of the factors influencing data quality and project efficacy. Patterns of contributor effort and task performance have been well reviewe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,meta分析
doi:10.1073/pnas.1807186115
更新日期:2019-02-05 00:00:00
abstract::Antibodies specific for allelic determinants of the cell membrane alloantigen Ly-17 were found to react with genetically determined polymorphic sites on the murine IgG Fc receptor (Fc gamma R). Monoclonal antibodies specific for Ly-17.2 and the Fc gamma R detected identical populations of cells in thymus, spleen, lymp...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.22.7706
更新日期:1985-11-01 00:00:00
abstract::We provide empirical evidence of immigrants' specialization in skill acquisition well before entering the US labor market. Nationally representative datasets enable studying the academic trajectories of immigrant children, with a focus on high-school course-taking patterns and college major choice. Immigrant children ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1812041116
更新日期:2019-01-08 00:00:00
abstract::An effective metabolism is essential to all living organisms, including the important human pathogen Staphylococcus aureus. To establish successful infection, S. aureus must scavenge nutrients and coordinate its metabolism for proliferation. Meanwhile, it also must produce an array of virulence factors to interfere wi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1411077111
更新日期:2014-11-18 00:00:00
abstract::Mitochondrial DNA from several mammalian species has been digested with a site-specific restriction endonuclease (HaeIII) from Haemophilus aegyptius. A quantitative analysis of the resulting specific fragments indicates that the mtDNA of any individual mammal is predominantly a single molecular clone. Gel analysis of ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.11.4496
更新日期:1975-11-01 00:00:00
abstract::The cat tongue is covered in sharp, rear-facing spines called papillae, the precise function of which is a mystery. In this combined experimental and theoretical study, we use high-speed film, grooming force measurements, and computed tomography (CT) scanning to elucidate the mechanism by which papillae are used to gr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1809544115
更新日期:2018-12-04 00:00:00
abstract::It has been known for more than a century that increases in neuronal activity in the brain are reliably accompanied by changes in local blood flow. More recently it has been appreciated that these blood flow increases are accompanied by increases in glycolysis that are much greater than the increases in oxidative phos...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0510632103
更新日期:2006-02-07 00:00:00
abstract::By exploiting the ability of Pseudomonas aeruginosa to infect a variety of vertebrate and nonvertebrate hosts, we have developed model systems that use plants and nematodes as adjuncts to mammalian models to help elucidate the molecular basis of P. aeruginosa pathogenesis. Our studies reveal a remarkable degree of con...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.97.16.8815
更新日期:2000-08-01 00:00:00
abstract::We present ab initio calculations of the phase diagram of liquid CO(2) and its melting curve over a wide range of pressure and temperature conditions, including those relevant to the Earth. Several distinct liquid phases are predicted up to 200 GPa and 10,000 K based on their structural and electronic characteristics....
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1120243109
更新日期:2012-09-11 00:00:00
abstract::We have previously reported that in four transcription factor families the DNA-recognition rules can be described as (i) chemical rules, which list possible pairings between the 20 amino acid residues and the four DNA bases, and (ii) stereochemical rules, which describe the base and amino acid positions in contact. We...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.26.12357
更新日期:1994-12-20 00:00:00
abstract::Current evidence favors the theory that, when the globular motor domain of myosin attaches to actin, the light chain binding domain or "lever arm" rotates, and thereby generates movement of actin filaments. Myosin is uniquely designed for such a role in that a long alpha-helix (approximately 9 nm) extending from the C...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0401699101
更新日期:2004-07-27 00:00:00
abstract::Tregs are essential for maintaining peripheral tolerance, and thus targeting these cells may aid in the treatment of autoimmunity and cancer by enhancing or reducing suppressive functions, respectively. Before these cells can be harnessed for therapeutic purposes, it is necessary to understand how they maintain tolera...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1605849113
更新日期:2016-08-09 00:00:00
abstract::Disruption of the blood-brain barrier (BBB) underlies the development of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis. Environmental factors, such as Bordetella pertussis, are thought to sensitize central endothelium to biogenic amines like histamine, thereby leading to increased BBB permeabi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1008816107
更新日期:2010-11-02 00:00:00
abstract::There are numerous studies on the immune response against malignant human tumors. This study was aimed to address the complexity and specificity of humoral immune response against a benign human tumor. We assembled a panel of 62 meningioma-expressed antigens that show reactivity with serum antibodies of meningioma pat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0500404102
更新日期:2005-07-05 00:00:00
abstract::We have constructed bovine papilloma virus recombinants carrying a hybrid gene in which human growth hormone structural sequences are fused to the promoter and presumptive control region of the mouse metallothionein-I gene. Mouse cells transformed with the recombinants synthesize metallothionein-growth hormone hybrid ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.2.397
更新日期:1983-01-01 00:00:00
abstract::We have identified a gene, rig (rat insulinoma gene), that is activated in chemically induced rat insulinomas but not in normal pancreatic islets or in regenerating islets. In the present study, we have found that the insulinoma gene was activated in a BK virus-induced hamster insulinoma cell line and in a spontaneous...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.19.6659
更新日期:1987-10-01 00:00:00
abstract::Skeletal muscle L-type Ca2+ channels respond to trains of brief depolarizations with a strong shift of the voltage dependence of channel activation toward more negative membrane potentials and slowing of channel deactivation. Increased Ca2+ entry resulting from this potentiation of channel activity may increase contra...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.24.11492
更新日期:1994-11-22 00:00:00
abstract::Mammalian nervous system function involves billions of neurons which are interconnected in a multitude of neural circuits. Here we describe a genetic approach to chart neural circuits. By using an olfactory-specific promoter, we selectively expressed barley lectin in sensory neurons in the olfactory epithelium and vom...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.6.3194
更新日期:1999-03-16 00:00:00
abstract::The mitochondrial genome of Saccharomyces cerevisiae codes for 24 tRNAs. The nucleotide sequences of the tRNA genes suggest a unique set of rules that govern the decoding of the mitochondrial genetic code. The four codons of unmixed fmilies are recognized by single tRNAs that always have a U in the wobble position of ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.6.3167
更新日期:1980-06-01 00:00:00
abstract::We describe a 98-base-pair region (-38 to +60) in the long terminal repeat of the Drosophila gypsy retrotransposon that is sufficient for accurate normal-level transcription. We find that, unlike most RNA polymerase II (pol II) promoters, the gypsy promoter includes downstream sequences that are required for full acti...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.1.102
更新日期:1991-01-01 00:00:00
abstract::When various wild strains of Penicillium lanosum and Aspergillus niger were placed in the same mild laboratory environment, their frequencies of new spontaneous mutations were clearly related to whether they had been isolated from a region of high or low microclimatic stress. In the mild environment, the total frequen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0801995105
更新日期:2008-04-15 00:00:00
abstract::A site that is preferentially cleaved by the single-strand-specific endonuclease from Aspergillus oryzae was located in vitro 180 base pairs upstream from the 5' end of the chicken pro-alpha 2(I) collagen gene. It is found in supercoiled plasmids with a negative superhelical density of -0.024 or more but not in linear...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.6.1659
更新日期:1984-03-01 00:00:00