Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons.

Abstract:

:Two mammalian genes, Kcnt1 and Kcnt2, encode pore-forming subunits of Na(+)-dependent K(+) (KNa) channels. Progress in understanding KNa channels has been hampered by the absence of specific tools and methods for rigorous KNa identification in native cells. Here, we report the genetic disruption of both Kcnt1 and Kcnt2, confirm the loss of Slo2.2 and Slo2.1 protein, respectively, in KO animals, and define tissues enriched in Slo2 expression. Noting the prevalence of Slo2.2 in dorsal root ganglion, we find that KO of Slo2.2, but not Slo2.1, results in enhanced itch and pain responses. In dissociated small diameter DRG neurons, KO of Slo2.2, but not Slo2.1, abolishes KNa current. Utilizing isolectin B4+ neurons, the absence of KNa current results in an increase in action potential (AP) firing and a decrease in AP threshold. Activation of KNa acts as a brake to initiation of the first depolarization-elicited AP with no discernible effect on afterhyperpolarizations.

journal_name

Elife

journal_title

eLife

authors

Martinez-Espinosa PL,Wu J,Yang C,Gonzalez-Perez V,Zhou H,Liang H,Xia XM,Lingle CJ

doi

10.7554/eLife.10013

subject

Has Abstract

pub_date

2015-11-11 00:00:00

issn

2050-084X

journal_volume

4

pub_type

杂志文章

相关文献

eLife文献大全
  • Targeting the link between late pregnancy and breast cancer.

    abstract::Why does a first pregnancy after age 35 increase the risk of breast cancer, and what can be done to combat this? ...

    journal_title:eLife

    pub_type: 评论,杂志文章

    doi:10.7554/eLife.01926

    authors: Chakravarthi BV,Varambally S

    更新日期:2013-12-31 00:00:00

  • Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells.

    abstract::Mechanical force is a determinant of Notch signalling but the mechanism of force detection and its coupling to Notch are unclear. We propose a role for Piezo1 channels, which are mechanically-activated non-selective cation channels. In cultured microvascular endothelial cells, Piezo1 channel activation by either shear...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.50684

    authors: Caolo V,Debant M,Endesh N,Futers TS,Lichtenstein L,Bartoli F,Parsonage G,Jones EA,Beech DJ

    更新日期:2020-06-02 00:00:00

  • The spinal cord is never at rest.

    abstract::Even when we are at rest, our spinal cords show spontaneous, yet well organised, fluctuations of activity that might reflect sensory and motor networks. ...

    journal_title:eLife

    pub_type: 评论,杂志文章

    doi:10.7554/eLife.03811

    authors: Eippert F,Tracey I

    更新日期:2014-08-05 00:00:00

  • Slowly folding surface extension in the prototypic avian hepatitis B virus capsid governs stability.

    abstract::Hepatitis B virus (HBV) is an important but difficult to study human pathogen. Most basics of the hepadnaviral life-cycle were unraveled using duck HBV (DHBV) as a model although DHBV has a capsid protein (CP) comprising ~260 rather than ~180 amino acids. Here we present high-resolution structures of several DHBV caps...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.57277

    authors: Makbul C,Nassal M,Böttcher B

    更新日期:2020-08-14 00:00:00

  • Sliding to the rescue of damaged DNA.

    abstract::Single-molecule imaging experiments have shed new light on the methods used by the enzyme RecA to align single- and double-stranded DNA so that double-strand breaks can be repaired. ...

    journal_title:eLife

    pub_type: 评论,杂志文章

    doi:10.7554/eLife.00347

    authors: Gibb B,Greene EC

    更新日期:2012-12-13 00:00:00

  • Doa10 is a membrane protein retrotranslocase in ER-associated protein degradation.

    abstract::In endoplasmic reticulum-associated protein degradation (ERAD), membrane proteins are ubiquitinated, extracted from the membrane, and degraded by the proteasome. The cytosolic ATPase Cdc48 drives extraction by pulling on polyubiquitinated substrates. How hydrophobic transmembrane (TM) segments are moved from the phosp...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.56945

    authors: Schmidt CC,Vasic V,Stein A

    更新日期:2020-06-26 00:00:00

  • Behavioural diversity of bonobo prey preference as a potential cultural trait.

    abstract::The importance of cultural processes to behavioural diversity in our closest living relatives is central to revealing the evolutionary origins of human culture. However, the bonobo is often overlooked as a candidate model. Further, a prominent critique to many examples of proposed animal cultures is premature exclusio...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.59191

    authors: Samuni L,Wegdell F,Surbeck M

    更新日期:2020-09-01 00:00:00

  • Thermal fluctuations of immature SOD1 lead to separate folding and misfolding pathways.

    abstract::Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving cytotoxic conformations of Cu, Zn superoxide dismutase (SOD1). A major challenge in understanding ALS disease pathology has been the identification and atomic-level characterization of these conformers. Here, we use a combination ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.07296

    authors: Sekhar A,Rumfeldt JA,Broom HR,Doyle CM,Bouvignies G,Meiering EM,Kay LE

    更新日期:2015-06-23 00:00:00

  • Evolutionary dynamics of incubation periods.

    abstract::The incubation period for typhoid, polio, measles, leukemia and many other diseases follows a right-skewed, approximately lognormal distribution. Although this pattern was discovered more than sixty years ago, it remains an open question to explain its ubiquity. Here, we propose an explanation based on evolutionary dy...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.30212

    authors: Ottino-Loffler B,Scott JG,Strogatz SH

    更新日期:2017-12-21 00:00:00

  • Synaptic input sequence discrimination on behavioral timescales mediated by reaction-diffusion chemistry in dendrites.

    abstract::Sequences of events are ubiquitous in sensory, motor, and cognitive function. Key computational operations, including pattern recognition, event prediction, and plasticity, involve neural discrimination of spatio-temporal sequences. Here, we show that synaptically-driven reaction-diffusion pathways on dendrites can pe...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.25827

    authors: Bhalla US

    更新日期:2017-04-19 00:00:00

  • Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate.

    abstract::Development of specialized cells and structures in the heart is regulated by spatially -restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, c...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.31515

    authors: Burkhard SB,Bakkers J

    更新日期:2018-02-05 00:00:00

  • Increasing β-catenin/Wnt3A activity levels drive mechanical strain-induced cell cycle progression through mitosis.

    abstract::Mechanical force and Wnt signaling activate β-catenin-mediated transcription to promote proliferation and tissue expansion. However, it is unknown whether mechanical force and Wnt signaling act independently or synergize to activate β-catenin signaling and cell division. We show that mechanical strain induced Src-depe...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.19799

    authors: Benham-Pyle BW,Sim JY,Hart KC,Pruitt BL,Nelson WJ

    更新日期:2016-10-26 00:00:00

  • Monosynaptic tracing maps brain-wide afferent oligodendrocyte precursor cell connectivity.

    abstract::Neurons form bona fide synapses with oligodendrocyte precursor cells (OPCs), but the circuit context of these neuron to OPC synapses remains incompletely understood. Using monosynaptically-restricted rabies virus tracing of OPC afferents, we identified extensive afferent synaptic inputs to OPCs residing in secondary m...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.49291

    authors: Mount CW,Yalçın B,Cunliffe-Koehler K,Sundaresh S,Monje M

    更新日期:2019-10-18 00:00:00

  • Is it possible to reconstruct an accurate cell lineage using CRISPR recorders?

    abstract::Cell lineages provide the framework for understanding how cell fates are decided during development. Describing cell lineages in most organisms is challenging; even a fruit fly larva has ~50,000 cells and a small mammal has >1 billion cells. Recently, the idea of applying CRISPR to induce mutations during development,...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.40292

    authors: Salvador-Martínez I,Grillo M,Averof M,Telford MJ

    更新日期:2019-01-28 00:00:00

  • Addressing selective reporting of experiments through predefined exclusion criteria.

    abstract::The pressure for every research article to tell a clear story often leads researchers in the life sciences to exclude experiments that 'did not work' when they write up their results. However, this practice can lead to reporting bias if the decisions about which experiments to exclude are taken after data have been co...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.56626

    authors: Neves K,Amaral OB

    更新日期:2020-05-22 00:00:00

  • Extrinsic activin signaling cooperates with an intrinsic temporal program to increase mushroom body neuronal diversity.

    abstract::Temporal patterning of neural progenitors leads to the sequential production of diverse neurons. To understand how extrinsic cues influence intrinsic temporal programs, we studied Drosophila mushroom body progenitors (neuroblasts) that sequentially produce only three neuronal types: γ, then α'β', followed by αβ. Oppos...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.58880

    authors: Rossi AM,Desplan C

    更新日期:2020-07-06 00:00:00

  • Searching for epilepsy's crystal ball.

    abstract::Multi-modal MRI techniques have identified biomarkers that could help to predict whether someone will develop epilepsy. ...

    journal_title:eLife

    pub_type: 评论,杂志文章

    doi:10.7554/eLife.29853

    authors: Gröhn O,Sierra A

    更新日期:2017-07-26 00:00:00

  • Casposase structure and the mechanistic link between DNA transposition and spacer acquisition by CRISPR-Cas.

    abstract::Key to CRISPR-Cas adaptive immunity is maintaining an ongoing record of invading nucleic acids, a process carried out by the Cas1-Cas2 complex that integrates short segments of foreign genetic material (spacers) into the CRISPR locus. It is hypothesized that Cas1 evolved from casposases, a novel class of transposases....

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.50004

    authors: Hickman AB,Kailasan S,Genzor P,Haase AD,Dyda F

    更新日期:2020-01-08 00:00:00

  • Adaptation in protein fitness landscapes is facilitated by indirect paths.

    abstract::The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two am...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.16965

    authors: Wu NC,Dai L,Olson CA,Lloyd-Smith JO,Sun R

    更新日期:2016-07-08 00:00:00

  • Sensitivity and kinetics of signal transmission at the first visual synapse differentially impact visually-guided behavior.

    abstract::In the retina, synaptic transmission between photoreceptors and downstream ON-bipolar neurons (ON-BCs) is mediated by a GPCR pathway, which plays an essential role in vision. However, the mechanisms that control signal transmission at this synapse and its relevance to behavior remain poorly understood. In this study w...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.06358

    authors: Sarria I,Pahlberg J,Cao Y,Kolesnikov AV,Kefalov VJ,Sampath AP,Martemyanov KA

    更新日期:2015-04-16 00:00:00

  • Conserved noncoding transcription and core promoter regulatory code in early Drosophila development.

    abstract::Multicellular development is driven by regulatory programs that orchestrate the transcription of protein-coding and noncoding genes. To decipher this genomic regulatory code, and to investigate the developmental relevance of noncoding transcription, we compared genome-wide promoter activity throughout embryogenesis in...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.29005

    authors: Batut PJ,Gingeras TR

    更新日期:2017-12-20 00:00:00

  • The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor.

    abstract::Innate lymphoid cells (ILCs) are recently identified lymphocytes that limit infection and promote tissue repair at mucosal surfaces. However, the pathways underlying ILC development remain unclear. Here we show that the transcription factor NFIL3 directs the development of a committed bone marrow precursor that differ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.04406

    authors: Yu X,Wang Y,Deng M,Li Y,Ruhn KA,Zhang CC,Hooper LV

    更新日期:2014-10-13 00:00:00

  • TORC2-Gad8-dependent myosin phosphorylation modulates regulation by calcium.

    abstract::Cells respond to changes in their environment through signaling networks that modulate cytoskeleton and membrane organization to coordinate cell-cycle progression, polarized cell growth and multicellular development. Here, we define a novel regulatory mechanism by which the motor activity and function of the fission y...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.51150

    authors: Baker K,Gyamfi IA,Mashanov GI,Molloy JE,Geeves MA,Mulvihill DP

    更新日期:2019-09-30 00:00:00

  • Serine phosphorylation regulates the P-type potassium pump KdpFABC.

    abstract::KdpFABC is an ATP-dependent K+ pump that ensures bacterial survival in K+-deficient environments. Whereas transcriptional activation of kdpFABC expression is well studied, a mechanism for down-regulation when K+ levels are restored has not been described. Here, we show that KdpFABC is inhibited when cells return to a ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.55480

    authors: Sweet ME,Zhang X,Erdjument-Bromage H,Dubey V,Khandelia H,Neubert TA,Pedersen BP,Stokes DL

    更新日期:2020-09-21 00:00:00

  • MicroRNAs down-regulate homologous recombination in the G1 phase of cycling cells to maintain genomic stability.

    abstract::Homologous recombination (HR)-mediated repair of DNA double-strand break (DSB)s is restricted to the post-replicative phases of the cell cycle. Initiation of HR in the G1 phase blocks non-homologous end joining (NHEJ) impairing DSB repair. Completion of HR in G1 cells can lead to the loss-of-heterozygosity (LOH), whic...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.02445

    authors: Choi YE,Pan Y,Park E,Konstantinopoulos P,De S,D'Andrea A,Chowdhury D

    更新日期:2014-04-30 00:00:00

  • Intermittent hypoxia mediated by TSP1 dependent on STAT3 induces cardiac fibroblast activation and cardiac fibrosis.

    abstract::Intermittent hypoxia (IH) is the predominant pathophysiological disturbance in obstructive sleep apnea (OSA), known to be independently associated with cardiovascular diseases. However, the effect of IH on cardiac fibrosis and molecular events involved in this process are unclear. Here, we tested IH in angiotensin II ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.49923

    authors: Bao Q,Zhang B,Suo Y,Liu C,Yang Q,Zhang K,Yuan M,Yuan M,Zhang Y,Li G

    更新日期:2020-01-14 00:00:00

  • Common concepts for bacterial collectives.

    abstract::The expansion of bacterial swarms and the spreading of biofilms can be described by a unified biophysical theory that involves both active and passive processes. ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.47019

    authors: Jeckel H,Matthey N,Drescher K

    更新日期:2019-04-30 00:00:00

  • Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in Drosophila.

    abstract::Brain connectivity maps display a delicate balance between individual variation and stereotypy, suggesting the existence of dedicated mechanisms that simultaneously permit and limit individual variation. We show that during the development of the Drosophila central nervous system, mutual inhibition among groups of nei...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.00337

    authors: Langen M,Koch M,Yan J,De Geest N,Erfurth ML,Pfeiffer BD,Schmucker D,Moreau Y,Hassan BA

    更新日期:2013-03-05 00:00:00

  • Blue light-induced LOV domain dimerization enhances the affinity of Aureochrome 1a for its target DNA sequence.

    abstract::The design of synthetic optogenetic tools that allow precise spatiotemporal control of biological processes previously inaccessible to optogenetic control has developed rapidly over the last years. Rational design of such tools requires detailed knowledge of allosteric light signaling in natural photoreceptors. To und...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.11860

    authors: Heintz U,Schlichting I

    更新日期:2016-01-12 00:00:00

  • Large-scale network integration in the human brain tracks temporal fluctuations in memory encoding performance.

    abstract::Although activation/deactivation of specific brain regions has been shown to be predictive of successful memory encoding, the relationship between time-varying large-scale brain networks and fluctuations of memory encoding performance remains unclear. Here, we investigated time-varying functional connectivity patterns...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.32696

    authors: Keerativittayayut R,Aoki R,Sarabi MT,Jimura K,Nakahara K

    更新日期:2018-06-18 00:00:00