Trpm4 ion channels in pre-Bötzinger complex interneurons are essential for breathing motor pattern but not rhythm.

Abstract:

:Inspiratory breathing movements depend on pre-Bötzinger complex (preBötC) interneurons that express calcium (Ca2+)-activated nonselective cationic current (ICAN) to generate robust neural bursts. Hypothesized to be rhythmogenic, reducing ICAN is predicted to slow down or stop breathing; its contributions to motor pattern would be reflected in the magnitude of movements (output). We tested the role(s) of ICAN using reverse genetic techniques to diminish its putative ion channels Trpm4 or Trpc3 in preBötC neurons in vivo. Adult mice transduced with Trpm4-targeted short hairpin RNA (shRNA) progressively decreased the tidal volume of breaths yet surprisingly increased breathing frequency, often followed by gasping and fatal respiratory failure. Mice transduced with Trpc3-targeted shRNA survived with no changes in breathing. Patch-clamp and field recordings from the preBötC in mouse slices also showed an increase in the frequency and a decrease in the magnitude of preBötC neural bursts in the presence of Trpm4 antagonist 9-phenanthrol, whereas the Trpc3 antagonist pyrazole-3 (pyr-3) showed inconsistent effects on magnitude and no effect on frequency. These data suggest that Trpm4 mediates ICAN, whose influence on frequency contradicts a direct role in rhythm generation. We conclude that Trpm4-mediated ICAN is indispensable for motor output but not the rhythmogenic core mechanism of the breathing central pattern generator.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Picardo MCD,Sugimura YK,Dorst KE,Kallurkar PS,Akins VT,Ma X,Teruyama R,Guinamard R,Kam K,Saha MS,Del Negro CA

doi

10.1371/journal.pbio.2006094

subject

Has Abstract

pub_date

2019-02-21 00:00:00

pages

e2006094

issue

2

eissn

1544-9173

issn

1545-7885

pii

pbio.2006094

journal_volume

17

pub_type

杂志文章
  • Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans.

    abstract::Prior studies have shown that disruption of mitochondrial electron transport chain (ETC) function in the nematode Caenorhabditis elegans can result in life extension. Counter to these findings, many mutations that disrupt ETC function in humans are known to be pathologically life-shortening. In this study, we have und...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0050259

    authors: Rea SL,Ventura N,Johnson TE

    更新日期:2007-10-02 00:00:00

  • Hyperexpansion of RNA Bacteriophage Diversity.

    abstract::Bacteriophage modulation of microbial populations impacts critical processes in ocean, soil, and animal ecosystems. However, the role of bacteriophages with RNA genomes (RNA bacteriophages) in these processes is poorly understood, in part because of the limited number of known RNA bacteriophage species. Here, we ident...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002409

    authors: Krishnamurthy SR,Janowski AB,Zhao G,Barouch D,Wang D

    更新日期:2016-03-24 00:00:00

  • ATPase-dependent control of the Mms21 SUMO ligase during DNA repair.

    abstract::Modification of proteins by SUMO is essential for the maintenance of genome integrity. During DNA replication, the Mms21-branch of the SUMO pathway counteracts recombination intermediates at damaged replication forks, thus facilitating sister chromatid disjunction. The Mms21 SUMO ligase docks to the arm region of the ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002089

    authors: Bermúdez-López M,Pociño-Merino I,Sánchez H,Bueno A,Guasch C,Almedawar S,Bru-Virgili S,Garí E,Wyman C,Reverter D,Colomina N,Torres-Rosell J

    更新日期:2015-03-12 00:00:00

  • Widespread Genetic Incompatibilities between First-Step Mutations during Parallel Adaptation of Saccharomyces cerevisiae to a Common Environment.

    abstract::Independently evolving populations may adapt to similar selection pressures via different genetic changes. The interactions between such changes, such as in a hybrid individual, can inform us about what course adaptation may follow and allow us to determine whether gene flow would be facilitated or hampered following ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002591

    authors: Ono J,Gerstein AC,Otto SP

    更新日期:2017-01-23 00:00:00

  • The Grand Convergence: Closing the Divide between Public Health Funding and Global Health Needs.

    abstract::The Global Health 2035 report notes that the "grand convergence"--closure of the infectious, maternal, and child mortality gap between rich and poor countries--is dependent on research and development (R&D) of new drugs, vaccines, diagnostics, and other health tools. However, this convergence (and the R&D underpinning...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002363

    authors: Moran M

    更新日期:2016-03-02 00:00:00

  • Selection of motor programs for suppressing food intake and inducing locomotion in the Drosophila brain.

    abstract::Central mechanisms by which specific motor programs are selected to achieve meaningful behaviors are not well understood. Using electrophysiological recordings from pharyngeal nerves upon central activation of neurotransmitter-expressing cells, we show that distinct neuronal ensembles can regulate different feeding mo...

    journal_title:PLoS biology

    pub_type: 评论,杂志文章

    doi:10.1371/journal.pbio.1001893

    authors: Schoofs A,Hückesfeld S,Schlegel P,Miroschnikow A,Peters M,Zeymer M,Spieß R,Chiang AS,Pankratz MJ

    更新日期:2014-06-24 00:00:00

  • Alerting or Somnogenic Light: Pick Your Color.

    abstract::In mammals, light exerts pervasive effects on physiology and behavior in two ways: indirectly through clock synchronization and the phase adjustment of circadian rhythms, and directly through the promotion of alertness and sleep, respectively, in diurnal and nocturnal species. A recent report by Pilorz and colleagues ...

    journal_title:PLoS biology

    pub_type: 评论,杂志文章

    doi:10.1371/journal.pbio.2000111

    authors: Bourgin P,Hubbard J

    更新日期:2016-08-15 00:00:00

  • Authentication: A Standard Problem or a Problem of Standards?

    abstract::Reproducibility and transparency in biomedical sciences have been called into question, and scientists have been found wanting as a result. Putting aside deliberate fraud, there is evidence that a major contributor to lack of reproducibility is insufficient quality assurance of reagents used in preclinical research. C...

    journal_title:PLoS biology

    pub_type: 评论,杂志文章

    doi:10.1371/journal.pbio.1002477

    authors: Capes-Davis A,Neve RM

    更新日期:2016-06-14 00:00:00

  • Placental chemokine compartmentalisation: A novel mammalian molecular control mechanism.

    abstract::Atypical chemokine receptor 2 (ACKR2) is a chemokine-scavenging receptor. ACKR2-/-embryos display a reduction in size of a novel, to our knowledge, embryonic skin macrophage population referred to as 'intermediate' cells. CC chemokine receptor 2 (CCR2)-/-embryos display an identical phenotype, indicating that these ce...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000287

    authors: Lee KM,Wilson GJ,Pingen M,Fukuoka A,Hansell CAH,Bartolini R,Medina-Ruiz L,Graham GJ

    更新日期:2019-05-29 00:00:00

  • Modulating brain oscillations to drive brain function.

    abstract::Do neuronal oscillations play a causal role in brain function? In a study in this issue of PLOS Biology, Helfrich and colleagues address this long-standing question by attempting to drive brain oscillations using transcranial electrical current stimulation. Remarkably, they were able to manipulate visual perception by...

    journal_title:PLoS biology

    pub_type: 评论,杂志文章

    doi:10.1371/journal.pbio.1002032

    authors: Thut G

    更新日期:2014-12-30 00:00:00

  • Dopamine modulates subcortical responses to surprising sounds.

    abstract::Dopamine guides behavior and learning through pleasure, according to classic understanding. Dopaminergic neurons are traditionally thought to signal positive or negative prediction errors (PEs) when reward expectations are, respectively, exceeded or not matched. These signed PEs are quite different from the unsigned P...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000744

    authors: Valdés-Baizabal C,Carbajal GV,Pérez-González D,Malmierca MS

    更新日期:2020-06-19 00:00:00

  • Genes, cells, and biobanks: Yes, there's still a consent problem.

    abstract::From a research perspective, the interest in biobanking continues to intensify. Governments and industry have invested heavily in biobanks, as exemplified by initiatives like the United Kingdom Biobank and United States' Precision Medicine Initiative. But despite this enthusiasm, many profound legal and ethical challe...

    journal_title:PLoS biology

    pub_type: 杂志文章,评审

    doi:10.1371/journal.pbio.2002654

    authors: Caulfield T,Murdoch B

    更新日期:2017-07-25 00:00:00

  • Oxidative stress inactivates cobalamin-independent methionine synthase (MetE) in Escherichia coli.

    abstract::In nature, Escherichia coli are exposed to harsh and non-ideal growth environments-nutrients may be limiting, and cells are often challenged by oxidative stress. For E. coli cells confronting these realities, there appears to be a link between oxidative stress, methionine availability, and the enzyme that catalyzes th...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0020336

    authors: Hondorp ER,Matthews RG

    更新日期:2004-11-01 00:00:00

  • Improving the trustworthiness, usefulness, and ethics of biomedical research through an innovative and comprehensive institutional initiative.

    abstract::The reproducibility crisis triggered worldwide initiatives to improve rigor, reproducibility, and transparency in biomedical research. There are many examples of scientists, journals, and funding agencies adopting responsible research practices. The QUEST (Quality-Ethics-Open Science-Translation) Center offers a uniqu...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000576

    authors: Strech D,Weissgerber T,Dirnagl U,QUEST Group.

    更新日期:2020-02-11 00:00:00

  • Heterochromatin delays CRISPR-Cas9 mutagenesis but does not influence the outcome of mutagenic DNA repair.

    abstract::Genome editing occurs in the context of chromatin, which is heterogeneous in structure and function across the genome. Chromatin heterogeneity is thought to affect genome editing efficiency, but this has been challenging to quantify due to the presence of confounding variables. Here, we develop a method that exploits ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.2005595

    authors: Kallimasioti-Pazi EM,Thelakkad Chathoth K,Taylor GC,Meynert A,Ballinger T,Kelder MJE,Lalevée S,Sanli I,Feil R,Wood AJ

    更新日期:2018-12-12 00:00:00

  • Commensal bacteria and essential amino acids control food choice behavior and reproduction.

    abstract::Choosing the right nutrients to consume is essential to health and wellbeing across species. However, the factors that influence these decisions are poorly understood. This is particularly true for dietary proteins, which are important determinants of lifespan and reproduction. We show that in Drosophila melanogaster,...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.2000862

    authors: Leitão-Gonçalves R,Carvalho-Santos Z,Francisco AP,Fioreze GT,Anjos M,Baltazar C,Elias AP,Itskov PM,Piper MDW,Ribeiro C

    更新日期:2017-04-25 00:00:00

  • Breast Cancer Patients Have Greatly Benefited from the Progress in Molecular Oncology.

    abstract::Cancer research has become a global enterprise, and the number of researchers, as well as the cost for their activities, has skyrocketed. The budget for the National Cancer Institute of the United States National Institutes of Health alone was US$5.2 billion in 2015. Since most of the research is funded by public mone...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.2000314

    authors: Groner BL,Hynes NE

    更新日期:2016-09-29 00:00:00

  • Adaptation, plasticity, and extinction in a changing environment: towards a predictive theory.

    abstract::Many species are experiencing sustained environmental change mainly due to human activities. The unusual rate and extent of anthropogenic alterations of the environment may exceed the capacity of developmental, genetic, and demographic mechanisms that populations have evolved to deal with environmental change. To begi...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1000357

    authors: Chevin LM,Lande R,Mace GM

    更新日期:2010-04-27 00:00:00

  • A systematic approach to pair secretory cargo receptors with their cargo suggests a mechanism for cargo selection by Erv14.

    abstract::The endoplasmic reticulum (ER) is the site of synthesis of secreted and membrane proteins. To exit the ER, proteins are packaged into COPII vesicles through direct interaction with the COPII coat or aided by specific cargo receptors. Despite the fundamental role of such cargo receptors in protein traffic, only a few h...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001329

    authors: Herzig Y,Sharpe HJ,Elbaz Y,Munro S,Schuldiner M

    更新日期:2012-01-01 00:00:00

  • Meta-research: Why research on research matters.

    abstract::Meta-research is the study of research itself: its methods, reporting, reproducibility, evaluation, and incentives. Given that science is the key driver of human progress, improving the efficiency of scientific investigation and yielding more credible and more useful research results can translate to major benefits. T...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.2005468

    authors: Ioannidis JPA

    更新日期:2018-03-13 00:00:00

  • Fbw7 repression by hes5 creates a feedback loop that modulates Notch-mediated intestinal and neural stem cell fate decisions.

    abstract::FBW7 is a crucial component of an SCF-type E3 ubiquitin ligase, which mediates degradation of an array of different target proteins. The Fbw7 locus comprises three different isoforms, each with its own promoter and each suspected to have a distinct set of substrates. Most FBW7 targets have important functions in devel...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001586

    authors: Sancho R,Blake SM,Tendeng C,Clurman BE,Lewis J,Behrens A

    更新日期:2013-01-01 00:00:00

  • Polarised asymmetric inheritance of accumulated protein damage in higher eukaryotes.

    abstract::Disease-associated misfolded proteins or proteins damaged due to cellular stress are generally disposed via the cellular protein quality-control system. However, under saturating conditions, misfolded proteins will aggregate. In higher eukaryotes, these aggregates can be transported to accumulate in aggresomes at the ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0040417

    authors: Rujano MA,Bosveld F,Salomons FA,Dijk F,van Waarde MA,van der Want JJ,de Vos RA,Brunt ER,Sibon OC,Kampinga HH

    更新日期:2006-12-01 00:00:00

  • The slings and arrows of comparative linguistics.

    abstract::In this Formal Comment the authors respond to objections to their previous Essay, reiterating that comparative linguistics is not an easy undertaking. ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000019

    authors: Bolhuis JJ,Beckers GJL,Huybregts MAC,Berwick RC,Everaert MBH

    更新日期:2018-09-24 00:00:00

  • Visual detection is locked to the internal dynamics of cortico-motor control.

    abstract::Movements overtly sample sensory information, making sensory analysis an active-sensing process. In this study, we show that visual information sampling is not just locked to the (overt) movement dynamics but to the internal (covert) dynamics of cortico-motor control. We asked human participants to perform continuous ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000898

    authors: Tomassini A,Maris E,Hilt P,Fadiga L,D'Ausilio A

    更新日期:2020-10-20 00:00:00

  • An immunological marker of tolerance to infection in wild rodents.

    abstract::Hosts are likely to respond to parasitic infections by a combination of resistance (expulsion of pathogens) and tolerance (active mitigation of pathology). Of these strategies, the basis of tolerance in animal hosts is relatively poorly understood, with especially little known about how tolerance is manifested in natu...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001901

    authors: Jackson JA,Hall AJ,Friberg IM,Ralli C,Lowe A,Zawadzka M,Turner AK,Stewart A,Birtles RJ,Paterson S,Bradley JE,Begon M

    更新日期:2014-07-08 00:00:00

  • One lipid, two synaptic plasticity pathways.

    abstract::A new study identifies an unexpected role for lysophosphatidic acid in modulating the strength of both excitatory and inhibitory synapses in the brain, but by different mechanisms. Read the accompanying Research Article. ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002154

    authors: Robinson R

    更新日期:2015-05-21 00:00:00

  • The bacterial effector HopX1 targets JAZ transcriptional repressors to activate jasmonate signaling and promote infection in Arabidopsis.

    abstract::Pathogenicity of Pseudomonas syringae is dependent on a type III secretion system, which secretes a suite of virulence effector proteins into the host cytoplasm, and the production of a number of toxins such as coronatine (COR), which is a mimic of the plant hormone jasmonate-isoleuce (JA-Ile). Inside the plant cell, ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001792

    authors: Gimenez-Ibanez S,Boter M,Fernández-Barbero G,Chini A,Rathjen JP,Solano R

    更新日期:2014-02-18 00:00:00

  • CDKN1B/p27 is localized in mitochondria and improves respiration-dependent processes in the cardiovascular system-New mode of action for caffeine.

    abstract::We show that the cyclin-dependent kinase inhibitor 1B (CDKN1B)/p27, previously known as a cell cycle inhibitor, is also localized within mitochondria. The migratory capacity of endothelial cells, which need intact mitochondria, is completely dependent on mitochondrial p27. Mitochondrial p27 improves mitochondrial memb...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.2004408

    authors: Ale-Agha N,Goy C,Jakobs P,Spyridopoulos I,Gonnissen S,Dyballa-Rukes N,Aufenvenne K,von Ameln F,Zurek M,Spannbrucker T,Eckermann O,Jakob S,Gorressen S,Abrams M,Grandoch M,Fischer JW,Köhrer K,Deenen R,Unfried K,Altsch

    更新日期:2018-06-21 00:00:00

  • ADAMTS13 maintains cerebrovascular integrity to ameliorate Alzheimer-like pathology.

    abstract::Blood-brain barrier (BBB) defects and cerebrovascular dysfunction contribute to amyloid-β (Aβ) brain accumulation and drive Alzheimer disease (AD) pathology. By regulating vascular functions and inflammation in the microvasculature, a disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS1...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000313

    authors: Cao Y,Xu H,Zhu Y,Shi MJ,Wei L,Zhang J,Cheng S,Shi Y,Tong H,Kang L,Lu L,Luo H,Yang X,Bai X,Wang R,Ma Y,Wang Y,Wang Z,Zhong K,Zhao BQ,Fan W

    更新日期:2019-06-11 00:00:00

  • New developmental evidence clarifies the evolution of wrist bones in the dinosaur-bird transition.

    abstract::From early dinosaurs with as many as nine wrist bones, modern birds evolved to develop only four ossifications. Their identity is uncertain, with different labels used in palaeontology and developmental biology. We examined embryos of several species and studied chicken embryos in detail through a new technique allowi...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001957

    authors: Botelho JF,Ossa-Fuentes L,Soto-Acuña S,Smith-Paredes D,Nuñez-León D,Salinas-Saavedra M,Ruiz-Flores M,Vargas AO

    更新日期:2014-09-30 00:00:00