Facilitation of murine cardiac L-type Ca(v)1.2 channel is modulated by calmodulin kinase II-dependent phosphorylation of S1512 and S1570.

Abstract:

:Activity-dependent means of altering calcium (Ca(2)(+)) influx are assumed to be of great physiological consequence, although definitive tests of this assumption have only begun to emerge. Facilitation and inactivation offer two opposing, activity-dependent means of altering Ca(2+) influx via cardiac Ca(v)1.2 calcium channels. Voltage- and frequency-dependent facilitation of Ca(v)1.2 has been reported to depend on Calmodulin (CaM) and/or the activity of Calmodulin kinase II (CaMKII). Several sites within the cardiac L-type calcium channel complex have been proposed as the targets of CaMKII. Here, we generated mice with knockin mutations of alpha(1)1.2 S1512 and S1570 phosphorylation sites [sine facilitation (SF) mice]. Homocygote SF mice were viable and reproduced in a Mendelian ratio. Voltage-dependent facilitation in ventricular cardiomyocytes carrying the SF mutation was decreased from 1.58- to 1.18-fold. The CaMKII inhibitor KN-93 reduced facilitation to 1.28 in control cardiomyocytes. SF mutation negatively shifted the voltage-dependent inactivation and slowed recovery from inactivation, thereby making fewer channels available for activation. Telemetric ECG recordings at different heart rates showed that QT time decreased significantly more in SF than in control mice at higher rates. Our results strongly support the notion that CaMKII-dependent phosphorylation of Cav1.2 at S1512 and S1570 mediates Ca(2+) current facilitation in the murine heart.

authors

Blaich A,Welling A,Fischer S,Wegener JW,Köstner K,Hofmann F,Moosmang S

doi

10.1073/pnas.0914287107

subject

Has Abstract

pub_date

2010-06-01 00:00:00

pages

10285-9

issue

22

eissn

0027-8424

issn

1091-6490

pii

0914287107

journal_volume

107

pub_type

杂志文章
  • Structure of rat BCKD kinase: nucleotide-induced domain communication in a mitochondrial protein kinase.

    abstract::Mitochondrial protein kinases (mPKs) are molecular switches that down-regulate the oxidation of branched-chain alpha-ketoacids and pyruvate. Elevated levels of these metabolites are implicated in disease states such as insulin-resistant Type II diabetes, branched-chain ketoaciduria, and primary lactic acidosis. We rep...

    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.201220098

    authors: Machius M,Chuang JL,Wynn RM,Tomchick DR,Chuang DT

    更新日期:2001-09-25 00:00:00

  • Crystal structure of Clostridium botulinum neurotoxin protease in a product-bound state: Evidence for noncanonical zinc protease activity.

    abstract::Clostridium botulinum neurotoxins (BoNTs), the most potent toxins known, disrupt neurotransmission through proteolysis of proteins involved in neuroexocytosis. The light chains of BoNTs are unique zinc proteases that have stringent substrate specificity and require exceptionally long substrates. We have determined the...

    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.0400584101

    authors: Segelke B,Knapp M,Kadkhodayan S,Balhorn R,Rupp B

    更新日期:2004-05-04 00:00:00

  • Induction by lithium ion of multiplication of mouse mammary epithelium in culture.

    abstract::Lithium ion at concentrations between 2 and 20 mM simulated the stimulatory effects of insulin on the uptake of alpha-aminoisobutyric acid, synthesis of RNA and DNA, and cell multiplication in mouse mammary gland explants cultured in a chemically defined synthetic medium. Other monovalent cations were virtually ineffe...

    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.76.6.2823

    authors: Hori C,Oka T

    更新日期:1979-06-01 00:00:00

  • Transcriptional organization of a 450-kb region of the human X chromosome in Xq28.

    abstract::In this paper, we report the transcriptional organization of a 450-kb gene cluster in Xq28, flanked by the glucose-6-phosphate dehydrogenase and the color vision genes. CpG islands previously identified and mapped to distal Xq28 have helped in construction of a continuous contig of cosmids and in identification of cDN...

    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.90.23.10977

    authors: Bione S,Tamanini F,Maestrini E,Tribioli C,Poustka A,Torri G,Rivella S,Toniolo D

    更新日期:1993-12-01 00:00:00

  • GABAB receptor deficiency causes failure of neuronal homeostasis in hippocampal networks.

    abstract::Stabilization of neuronal activity by homeostatic control systems is fundamental for proper functioning of neural circuits. Failure in neuronal homeostasis has been hypothesized to underlie common pathophysiological mechanisms in a variety of brain disorders. However, the key molecules regulating homeostasis in centra...

    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.1424810112

    authors: Vertkin I,Styr B,Slomowitz E,Ofir N,Shapira I,Berner D,Fedorova T,Laviv T,Barak-Broner N,Greitzer-Antes D,Gassmann M,Bettler B,Lotan I,Slutsky I

    更新日期:2015-06-23 00:00:00

  • Reconstructing a solid-solid phase transformation pathway in CdSe nanosheets with associated soft ligands.

    abstract::Integrated single-crystal-like small and wide-angle X-ray diffraction images of a CdSe nanosheet under pressure provide direct experimental evidence for the detailed pathway of transformation of the CdSe from a wurtzite to a rock-salt structure. Two consecutive planar atomic slips [(001) {110} in parallel and (102) {1...

    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.1011224107

    authors: Wang Z,Wen XD,Hoffmann R,Son JS,Li R,Fang CC,Smilgies DM,Hyeon T

    更新日期:2010-10-05 00:00:00

  • Use of site-directed mutagenesis to elucidate the role of arginine-166 in the catalytic mechanism of alkaline phosphatase.

    abstract::The guanidinium group of arginine-166 has been postulated to act as an electrophilic species during phosphorylation of alkaline phosphatase. Its role could be either to stabilize the developing negative charge on the oxygen of the leaving group or the pentacoordinate transition state or to help bind the -PO2-3 group. ...

    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.85.12.4276

    authors: Butler-Ransohoff JE,Kendall DA,Kaiser ET

    更新日期:1988-06-01 00:00:00

  • Translational control of specific uterine protein synthesis after estrogen induction.

    abstract::The rate of leucine incorporation into a specific estrogen-induced protein of immature rat isolated by gel electrophoresis declines rapidly between 2-4 hr after estrogen stimulation in vivo followed by incubation in vitro. Actinomycin D present during the in vitro phase prevents this decline, and elicits a "superinduc...

    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.70.1.18

    authors: DeAngelo AB,Fujimoto GI

    更新日期:1973-01-01 00:00:00

  • Quantitation of zidovudine-resistant human immunodeficiency virus type 1 in the blood of treated and untreated patients.

    abstract::A nonselective ex vivo assay was used to directly detect and quantify zidovudine (AZT)-resistant human immunodeficiency virus type 1 (HIV-1) in the blood of treated and untreated patients. In contrast to previous reports, drug-resistant virus was detected in peripheral blood mononuclear cells of a few of the patients ...

    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.90.1.25

    authors: Mohri H,Singh MK,Ching WT,Ho DD

    更新日期:1993-01-01 00:00:00

  • POU domain factor Brn-3b is required for the development of a large set of retinal ganglion cells.

    abstract::The three members of the Brn-3 family of POU domain transcription factors are found in highly restricted sets of central nervous system neurons. Within the retina, these factors are present only within subsets of ganglion cells. We show here that in the developing mouse retina, Brn-3b protein is first observed in pres...

    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.93.9.3920

    authors: Gan L,Xiang M,Zhou L,Wagner DS,Klein WH,Nathans J

    更新日期:1996-04-30 00:00:00

  • Mammalian Pumilio 2 regulates dendrite morphogenesis and synaptic function.

    abstract::In Drosophila, Pumilio (Pum) is important for neuronal homeostasis as well as learning and memory. We have recently characterized a mammalian homolog of Pum, Pum2, which is found in discrete RNA-containing particles in the somatodendritic compartment of polarized neurons. In this study, we investigated the role of Pum...

    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.0907128107

    authors: Vessey JP,Schoderboeck L,Gingl E,Luzi E,Riefler J,Di Leva F,Karra D,Thomas S,Kiebler MA,Macchi P

    更新日期:2010-02-16 00:00:00

  • A mechanism for slow release of biomagnified cyanobacterial neurotoxins and neurodegenerative disease in Guam.

    abstract::As root symbionts of cycad trees, cyanobacteria of the genus Nostoc produce beta-methylamino-l-alanine (BMAA), a neurotoxic nonprotein amino acid. The biomagnification of BMAA through the Guam ecosystem fits a classic triangle of increasing concentrations of toxic compounds up the food chain. However, because BMAA is ...

    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.0404926101

    authors: Murch SJ,Cox PA,Banack SA

    更新日期:2004-08-17 00:00:00

  • The diploid genome sequence of Candida albicans.

    abstract::We present the diploid genome sequence of the fungal pathogen Candida albicans. Because C. albicans has no known haploid or homozygous form, sequencing was performed as a whole-genome shotgun of the heterozygous diploid genome in strain SC5314, a clinical isolate that is the parent of strains widely used for molecular...

    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.0401648101

    authors: Jones T,Federspiel NA,Chibana H,Dungan J,Kalman S,Magee BB,Newport G,Thorstenson YR,Agabian N,Magee PT,Davis RW,Scherer S

    更新日期:2004-05-11 00:00:00

  • Protein structural and surface water rearrangement constitute major events in the earliest aggregation stages of tau.

    abstract::Protein aggregation plays a critical role in the pathogenesis of neurodegenerative diseases, and the mechanism of its progression is poorly understood. Here, we examine the structural and dynamic characteristics of transiently evolving protein aggregates under ambient conditions by directly probing protein surface wat...

    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.1504415113

    authors: Pavlova A,Cheng CY,Kinnebrew M,Lew J,Dahlquist FW,Han S

    更新日期:2016-01-12 00:00:00

  • Dual origin of mesenchymal stem cells contributing to organ growth and repair.

    abstract::In many adult tissues, mesenchymal stem cells (MSCs) are closely associated with perivascular niches and coexpress many markers in common with pericytes. The ability of pericytes to act as MSCs, however, remains controversial. By using genetic lineage tracing, we show that some pericytes differentiate into specialized...

    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.1015449108

    authors: Feng J,Mantesso A,De Bari C,Nishiyama A,Sharpe PT

    更新日期:2011-04-19 00:00:00

  • Energy-dependent processing of cytoplasmically made precursors to mitochondrial proteins.

    abstract::Earlier work has shown that mitochondrial proteins synthesized in the cytosol are initially made as larger precursors which are then transferred into the organelles and processed to their mature size in the absence of protein synthesis. It is now demonstrated that depletion of the mitochondrial matrix ATP in intact ye...

    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.76.9.4365

    authors: Nelson N,Schatz G

    更新日期:1979-09-01 00:00:00

  • Novel sensory adaptation mechanism in bacterial chemotaxis to oxygen and phosphotransferase substrates.

    abstract::The involvement of methylation in the chemosensory response of bacteria to many attractants has been clearly established by studies in several laboratories. It has been assumed that adaptation of Salmonella typhimurium and Escherichia coli to all attractants involves methylation of a transmembrane methyl-accepting che...

    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.79.1.11

    authors: Niwano M,Taylor BL

    更新日期:1982-01-01 00:00:00

  • 5'-Terminal sequences and coding region of late simian virus 40 mRNAs are derived from noncontiguous segments of the viral genome.

    abstract::The region of the simian virus 40 genome complementary to the 5' end of the most abundant poly(A)-containing 19S and 16S mRNAs was mapped by hybridization of double-labeled RNA ([3H]methyl group and [14C]uridine) to specific DNA fragments. Chemical identification of methylated residues indicated that a common "leader"...

    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.74.12.5323

    authors: Lavi S,Groner Y

    更新日期:1977-12-01 00:00:00

  • Ultrastructure of the first component of human complement: electron microscopy of the crosslinked complex.

    abstract::Electron micrographs are shown of the first component of human complement (C1) which has been crosslinked with a water-soluble carbodiimide to prevent dissociation into its C1q and C1r2C1s2 subunits. Two projections of the crosslinked molecule are seen in the electron micrographs, which are called "top" and "profile."...

    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.79.2.586

    authors: Strang CJ,Siegel RC,Phillips ML,Poon PH,Schumaker VN

    更新日期:1982-01-01 00:00:00

  • Plant hormone ethylene is a Norrish type II product from enzymically generated triplet 1-butanal.

    abstract::The peroxidase-catalyzed aerobic oxidation of a linear aldehyde, leading to the next lower homologue in the triplet state, is accompanied by Norrish type II product ethylene when the substrate is pentanal. This system appears to provide an example of "photobiochemistry without light" because ethylene is a plant hormon...

    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.91.1.410

    authors: Knudsen FD,Campa A,Stefani HA,Cilento G

    更新日期:1994-01-04 00:00:00

  • Protein quantification across hundreds of experimental conditions.

    abstract::Quantitative studies of protein abundance rarely span more than a small number of experimental conditions and replicates. In contrast, quantitative studies of transcript abundance often span hundreds of experimental conditions and replicates. This situation exists, in part, because extracting quantitative data from la...

    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.0904100106

    authors: Khan Z,Bloom JS,Garcia BA,Singh M,Kruglyak L

    更新日期:2009-09-15 00:00:00

  • Muscarinic stimulation of synaptic activity by protein kinase C is inhibited by adenosine in cultured hippocampal neurons.

    abstract::We have studied the effect of the cholinergic agonist carbachol on the spontaneous release of glutamate in cultured rat hippocampal cells. Spontaneous excitatory postsynaptic currents (sEPSCs) through glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type channels were recorded by means 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.94.22.12224

    authors: Bouron A,Reuter H

    更新日期:1997-10-28 00:00:00

  • Supermarket revolution in Asia and emerging development strategies to include small farmers.

    abstract::A "supermarket revolution" has occurred in developing countries in the past 2 decades. We focus on three specific issues that reflect the impact of this revolution, particularly in Asia: continuity in transformation, innovation in transformation, and unique development strategies. First, the record shows that the rapi...

    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.1003160108

    authors: Reardon T,Timmer CP,Minten B

    更新日期:2012-07-31 00:00:00

  • Correlation of individual papilloma latency time with DNA adducts, 8-hydroxy-2'-deoxyguanosine, and the rate of DNA synthesis in the epidermis of mice treated with 7,12-dimethylbenz[alpha]anthracene.

    abstract::The question was addressed whether the risk of cancer of an individual in a heterogeneous population can be predicted on the basis of measurable biochemical and biological variables postulated to be associated with the process of chemical carcinogenesis. Using the skin tumor model with outbred male NMRI mice, the late...

    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.92.13.5900

    authors: Fischer WH,Lutz WK

    更新日期:1995-06-20 00:00:00

  • Induction of NAD(P)H:quinone reductase in murine hepatoma cells by phenolic antioxidants, azo dyes, and other chemoprotectors: a model system for the study of anticarcinogens.

    abstract::Exposure of murine hepatoma (Hepa 1c1c7) cells to a variety of chemical agents known to protect animals against the neoplastic, mutagenic, and other toxic effects of chemical carcinogens results in dose- and time-dependent inductions of NAD(P)H:quinone reductase (EC 1.6.99.2). This enzyme protects against quinone toxi...

    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.83.3.787

    authors: De Long MJ,Prochaska HJ,Talalay P

    更新日期:1986-02-01 00:00:00

  • Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain.

    abstract::New neurons are continuously generated in restricted regions of the adult mammalian brain. Although these adult-born neurons have been shown to receive synaptic inputs, little is known about their synaptic outputs. Using retrovirus-mediated birth-dating and labeling in combination with serial section electron microsco...

    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.0806658105

    authors: Faulkner RL,Jang MH,Liu XB,Duan X,Sailor KA,Kim JY,Ge S,Jones EG,Ming GL,Song H,Cheng HJ

    更新日期:2008-09-16 00:00:00

  • Reductions in emissions from deforestation from Indonesia's moratorium on new oil palm, timber, and logging concessions.

    abstract::To reduce greenhouse gas emissions from deforestation, Indonesia instituted a nationwide moratorium on new license areas ("concessions") for oil palm plantations, timber plantations, and logging activity on primary forests and peat lands after May 2011. Here we indirectly evaluate the effectiveness of this policy usin...

    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.1412514112

    authors: Busch J,Ferretti-Gallon K,Engelmann J,Wright M,Austin KG,Stolle F,Turubanova S,Potapov PV,Margono B,Hansen MC,Baccini A

    更新日期:2015-02-03 00:00:00

  • Considerations of the concept of structural homology as applied to bovine carboxypeptidases A and B.

    abstract::An argument is presented in favor of the hypothesis that, bovine carboxypeptidases A and B fit by and large, the concept of homology on the levels of both amino acid sequence and three-dimensional structure. Two peptide sequences from carboxypeptidases A and B, comprising 46 amino acid residues, display structural hom...

    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.63.2.406

    authors: Bradshaw RA,Neurath H,Walsh KA

    更新日期:1969-06-01 00:00:00

  • Synthesis and in vivo murine evaluation of Na4[1-(1'-B10H9)-6-SHB10H8] as a potential agent for boron neutron capture therapy.

    abstract::Reaction of the normal isomer of [B20H18]2- and the protected thiol anion, [SC(O)OC(CH3)3]-, produces an unexpected isomer of [B20H17SC(O)OC(CH3)3]4- directly and in good yield. The isomer produced under mild conditions is characterized by an apical-apical boron atom intercage connection as well as the location of the...

    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.96.11.6406

    authors: Feakes DA,Waller RC,Hathaway DK,Morton VS

    更新日期:1999-05-25 00:00:00

  • Selective fertilization with phosphite allows unhindered growth of cotton plants expressing the ptxD gene while suppressing weeds.

    abstract::Weeds, which have been the bane of agriculture since the beginning of civilization, are managed manually, mechanically, and, more recently, by chemicals. However, chemical control options are rapidly shrinking due to the recent rise in the number of herbicide-resistant weeds in crop fields, with few alternatives on th...

    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.1804862115

    authors: Pandeya D,López-Arredondo DL,Janga MR,Campbell LM,Estrella-Hernández P,Bagavathiannan MV,Herrera-Estrella L,Rathore KS

    更新日期:2018-07-17 00:00:00