Mechanism of Ca(2+)-sensitive inactivation of L-type Ca2+ channels.


:Many high threshold, voltage-gated Ca2+ channels, including the dihydropyridine-sensitive class (L-type), inactivate in response not only to voltage, but also to entry of Ca2+. Despite the physiological importance of this Ca(2+)-sensitive inactivation, its molecular mechanism is understood only in broad outline. We now demonstrate that Ca(2+)-dependent inactivation transpires by a Ca(2+)-induced shift of channel gating to a low open probability mode, distinguished by a more than 100-fold reduction of entry rate to the open state. A gating mechanism that explains this shift quantitatively and enables successful separation of Ca(2+)- and voltage-sensitive forms of inactivation is deduced and tested. Finally, both calmodulin activation and channel (de)phosphorylation are excluded as significant signaling events underlying Ca(2+)-induced mode shifts, leaving direct binding of Ca2+ to the channel as a likely chemical initiation event for inactivation.






Imredy JP,Yue DT




Has Abstract


1994-06-01 00:00:00
















  • Glial cells of the oligodendrocyte lineage express both kainate- and AMPA-preferring subtypes of glutamate receptor.

    abstract::mRNAs for AMPA- and kainate-preferring glutamate receptor subunits are expressed abundantly in the CNS, yet functional studies of neurons and glia from brain suggest selective expression of AMPA receptors. We now show that glial cells of the O-2A lineage express rapidly desensitizing responses to kainate, mRNAs for Gl...


    pub_type: 杂志文章


    authors: Patneau DK,Wright PW,Winters C,Mayer ML,Gallo V

    更新日期:1994-02-01 00:00:00

  • From Healthcare to Warfare and Reverse: How Should We Regulate Dual-Use Neurotechnology?

    abstract::Recent advances in military-funded neurotechnology and novel opportunities for misusing neurodevices show that the problem of dual use is inherent to neuroscience. This paper discusses how the neuroscience community should respond to these dilemmas and delineates a neuroscience-specific biosecurity framework. This neu...


    pub_type: 杂志文章,评审


    authors: Ienca M,Jotterand F,Elger BS

    更新日期:2018-01-17 00:00:00

  • A Meta-Analysis Suggests Different Neural Correlates for Implicit and Explicit Learning.

    abstract::A meta-analysis of non-human primates performing three different tasks (Object-Match, Category-Match, and Category-Saccade associations) revealed signatures of explicit and implicit learning. Performance improved equally following correct and error trials in the Match (explicit) tasks, but it improved more after corre...


    pub_type: 杂志文章,meta分析


    authors: Loonis RF,Brincat SL,Antzoulatos EG,Miller EK

    更新日期:2017-10-11 00:00:00

  • Lack of evidence that myelin-associated glycoprotein is a major inhibitor of axonal regeneration in the CNS.

    abstract::The MAG-deficient mouse was used to test whether MAG acts as a significant inhibitor of axonal regeneration in the adult mammalian CNS, as suggested by cell culture experiments. Cell spreading, neurite elongation, or growth cone collapse of different cell types in vitro was not significantly different when myelin prep...


    pub_type: 杂志文章


    authors: Bartsch U,Bandtlow CE,Schnell L,Bartsch S,Spillmann AA,Rubin BP,Hillenbrand R,Montag D,Schwab ME,Schachner M

    更新日期:1995-12-01 00:00:00

  • A neuropeptide-mediated stretch response links muscle contraction to changes in neurotransmitter release.

    abstract::Although Caenorhabditis elegans has been utilized extensively to study synapse formation and function, relatively little is known about synaptic plasticity in C. elegans. We show that a brief treatment with the cholinesterase inhibitor aldicarb induces a form of presynaptic potentiation whereby ACh release at neuromus...


    pub_type: 杂志文章


    authors: Hu Z,Pym EC,Babu K,Vashlishan Murray AB,Kaplan JM

    更新日期:2011-07-14 00:00:00

  • Nucleus Accumbens Subnuclei Regulate Motivated Behavior via Direct Inhibition and Disinhibition of VTA Dopamine Subpopulations.

    abstract::Mesolimbic dopamine (DA) neurons play a central role in motivation and reward processing. Although the activity of these mesolimbic DA neurons is controlled by afferent inputs, little is known about the circuits in which they are embedded. Using retrograde tracing, electrophysiology, optogenetics, and behavioral assay...


    pub_type: 杂志文章


    authors: Yang H,de Jong JW,Tak Y,Peck J,Bateup HS,Lammel S

    更新日期:2018-01-17 00:00:00

  • Disruption of dopamine neuron activity pattern regulation through selective expression of a human KCNN3 mutation.

    abstract::The calcium-activated small conductance potassium channel SK3 plays an essential role in the regulation of dopamine neuron activity patterns. Here we demonstrate that expression of a human disease-related SK3 mutation (hSK3Δ) in dopamine neurons of mice disrupts the balance between tonic and phasic dopamine neuron act...


    pub_type: 杂志文章


    authors: Soden ME,Jones GL,Sanford CA,Chung AS,Güler AD,Chavkin C,Luján R,Zweifel LS

    更新日期:2013-11-20 00:00:00

  • Soma-Targeted Imaging of Neural Circuits by Ribosome Tethering.

    abstract::Neuroscience relies on techniques for imaging the structure and dynamics of neural circuits, but the cell bodies of individual neurons are often obscured by overlapping fluorescence from axons and dendrites in surrounding neuropil. Here, we describe two strategies for using the ribosome to restrict the expression of f...


    pub_type: 杂志文章


    authors: Chen Y,Jang H,Spratt PWE,Kosar S,Taylor DE,Essner RA,Bai L,Leib DE,Kuo TW,Lin YC,Patel M,Subkhangulova A,Kato S,Feinberg EH,Bender KJ,Knight ZA,Garrison JL

    更新日期:2020-08-05 00:00:00

  • BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer's disease.

    abstract::In recent years, nerve growth factor (NGF) has gained attention as a potential therapeutic agent for Alzheimer's disease (AD). To study the expression of NGF and its homologs, brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3), postmortem samples of hippocampus from AD and control donors were examined ...


    pub_type: 杂志文章


    authors: Phillips HS,Hains JM,Armanini M,Laramee GR,Johnson SA,Winslow JW

    更新日期:1991-11-01 00:00:00

  • Astrocytic ApoE reprograms neuronal cholesterol metabolism and histone-acetylation-mediated memory.

    abstract::Astrocytes metabolically interact with neighboring neurons by providing multiple substances to neurons. How astrocytes regulate neural functions via altering the neuronal metabolic state remains elusive. Here, we demonstrate that astrocytic ApoE vectors a variety of microRNAs (miRNAs), and these miRNAs specifically si...


    pub_type: 杂志文章


    authors: Li X,Zhang J,Li D,He C,He K,Xue T,Wan L,Zhang C,Liu Q

    更新日期:2021-01-21 00:00:00

  • Orientation preference patterns in mammalian visual cortex: a wire length minimization approach.

    abstract::In the visual cortex of many mammals, orientation preference changes smoothly along the cortical surface, with the exception of singularities such as pinwheels and fractures. The reason for the existence of these singularities has remained elusive, suggesting that they are developmental artifacts. We show that singula...


    pub_type: 杂志文章


    authors: Koulakov AA,Chklovskii DB

    更新日期:2001-02-01 00:00:00

  • Intersubunit contacts governing assembly of the mammalian nicotinic acetylcholine receptor.

    abstract::Through specific intersubunit contacts, the four subunits of the nicotinic acetylcholine receptor assemble into an alpha 2 beta gamma delta pentamer. The specificity of subunit association leads to formation of proper ligand binding sites and to transport of assembled pentamers to the cell surface. To identify determi...


    pub_type: 杂志文章


    authors: Kreienkamp HJ,Maeda RK,Sine SM,Taylor P

    更新日期:1995-03-01 00:00:00

  • A key role of starburst amacrine cells in originating retinal directional selectivity and optokinetic eye movement.

    abstract::The directional selectivity of retinal ganglion cell responses represents a primitive pattern recognition that operates within a retinal neural circuit. The cellular origin and mechanism of directional selectivity were investigated by selectively eliminating retinal starburst amacrine cells, using immunotoxin-mediated...


    pub_type: 杂志文章


    authors: Yoshida K,Watanabe D,Ishikane H,Tachibana M,Pastan I,Nakanishi S

    更新日期:2001-06-01 00:00:00

  • A Cre-dependent, anterograde transsynaptic viral tracer for mapping output pathways of genetically marked neurons.

    abstract::Neurotropic viruses that conditionally infect or replicate in molecularly defined neuronal subpopulations, and then spread transsynaptically, are powerful tools for mapping neural pathways. Genetically targetable retrograde transsynaptic tracer viruses are available to map the inputs to specific neuronal subpopulation...


    pub_type: 杂志文章


    authors: Lo L,Anderson DJ

    更新日期:2011-12-22 00:00:00

  • Initiation and spread of sodium action potentials in cerebellar Purkinje cells.

    abstract::Simultaneous whole-cell recordings were made from the soma and dendrites of cerebellar Purkinje cells in rat brain slices. Sodium action potentials, evoked by either depolarizing current pulses or synaptic stimulation of parallel or climbing fibers, always occurred first at the soma and decreased in amplitude with inc...


    pub_type: 杂志文章


    authors: Stuart G,Häusser M

    更新日期:1994-09-01 00:00:00

  • Calcium dependence of exo- and endocytotic coupling at a glutamatergic synapse.

    abstract::The mechanism coupling exocytosis and endocytosis remains to be elucidated at central synapses. Here, we show that the mechanism linking these two processes is dependent on microdomain-[Ca2+](i) similar to that which triggers exocytosis, as well as the exocytotic protein synaptobrevin/VAMP. Furthermore, block of endoc...


    pub_type: 杂志文章


    authors: Hosoi N,Holt M,Sakaba T

    更新日期:2009-07-30 00:00:00

  • Retinal coding of visual scenes -- repetitive and redundant too?

    abstract::Visual information reaches the brain by way of a fine cable, the optic nerve. The million or so axons in the optic nerve represent an information bottleneck in the visual pathway-where the fewest number of neurons convey the visual scene. It has long been thought that to make the most of the optic nerve's limited capa...


    pub_type: 评论,杂志文章,评审


    authors: Mukamel EA,Schnitzer MJ

    更新日期:2005-05-05 00:00:00

  • Spontaneous Synaptic Activation of Muscarinic Receptors by Striatal Cholinergic Neuron Firing.

    abstract::Cholinergic interneurons (CHIs) play a major role in motor and learning functions of the striatum. As acetylcholine does not directly evoke postsynaptic events at most striatal synapses, it remains unclear how postsynaptic cholinergic receptors encode the firing patterns of CHIs in the striatum. To examine the dynamic...


    pub_type: 杂志文章


    authors: Mamaligas AA,Ford CP

    更新日期:2016-08-03 00:00:00

  • GABAergic inhibition regulates developmental synapse elimination in the cerebellum.

    abstract::Functional neural circuit formation during development involves massive elimination of redundant synapses. In the cerebellum, one-to-one connection from excitatory climbing fiber (CF) to Purkinje cell (PC) is established by elimination of early-formed surplus CFs. This process depends on glutamatergic excitatory input...


    pub_type: 杂志文章


    authors: Nakayama H,Miyazaki T,Kitamura K,Hashimoto K,Yanagawa Y,Obata K,Sakimura K,Watanabe M,Kano M

    更新日期:2012-04-26 00:00:00

  • Dysregulation of striatal dopamine signaling by amphetamine inhibits feeding by hungry mice.

    abstract::Amphetamine (AMPH) releases monoamines, transiently stimulates locomotion, and inhibits feeding. Using a genetic approach, we show that mice lacking dopamine (DA-deficient, or DD, mice) are resistant to the hypophagic effects of a moderate dose of AMPH (2 microg/g) but manifest normal AMPH-induced hypophagia after res...


    pub_type: 杂志文章


    authors: Cannon CM,Abdallah L,Tecott LH,During MJ,Palmiter RD

    更新日期:2004-10-28 00:00:00

  • Primary structure and functional expression of a mammalian skeletal muscle sodium channel.

    abstract::We describe the isolation and characterization of a cDNA encoding the alpha subunit of a new voltage-sensitive sodium channel, microI, from rat skeletal muscle. The 1840 amino acid microI peptide is homologous to alpha subunits from rat brain, but, like the protein from eel electroplax, lacks an extended (approximatel...


    pub_type: 杂志文章


    authors: Trimmer JS,Cooperman SS,Tomiko SA,Zhou JY,Crean SM,Boyle MB,Kallen RG,Sheng ZH,Barchi RL,Sigworth FJ

    更新日期:1989-07-01 00:00:00

  • Apoptosis: final common pathway of photoreceptor death in rd, rds, and rhodopsin mutant mice.

    abstract::Mutations in the retinal degeneration, retinal degeneration slow(/peripherin) and rhodopsin genes cause photoreceptor degeneration in humans and mice. Although the phenotypes arising from these mutations are different, suggesting different mechanisms of pathogenesis, we present evidence that apoptosis may be the final...


    pub_type: 杂志文章


    authors: Chang GQ,Hao Y,Wong F

    更新日期:1993-10-01 00:00:00

  • Distinct Nanoscale Calcium Channel and Synaptic Vesicle Topographies Contribute to the Diversity of Synaptic Function.

    abstract::The nanoscale topographical arrangement of voltage-gated calcium channels (VGCC) and synaptic vesicles (SVs) determines synaptic strength and plasticity, but whether distinct spatial distributions underpin diversity of synaptic function is unknown. We performed single bouton Ca2+ imaging, Ca2+ chelator competition, im...


    pub_type: 杂志文章


    authors: Rebola N,Reva M,Kirizs T,Szoboszlay M,Lőrincz A,Moneron G,Nusser Z,DiGregorio DA

    更新日期:2019-11-20 00:00:00

  • Using Grid Cells for Navigation.

    abstract::Mammals are able to navigate to hidden goal locations by direct routes that may traverse previously unvisited terrain. Empirical evidence suggests that this "vector navigation" relies on an internal representation of space provided by the hippocampal formation. The periodic spatial firing patterns of grid cells in the...


    pub_type: 杂志文章,评审


    authors: Bush D,Barry C,Manson D,Burgess N

    更新日期:2015-08-05 00:00:00

  • Two-back makes step forward in brain imaging genomics.

    abstract::The combination of brain imaging and genetics promises to identify neural mechanisms underlying complex traits such as cognition and psychiatric disorder. The study by Heck et al. (2014) in this issue of Neuron highlights voltage-gated cation channel activity as a likely link and culprit. ...


    pub_type: 评论,杂志文章


    authors: McIntosh A,Deary I,Porteous DJ

    更新日期:2014-03-05 00:00:00

  • Structure of the RCK domain from the E. coli K+ channel and demonstration of its presence in the human BK channel.

    abstract::The intracellular C-terminal domain structure of a six-transmembrane K+ channel from Escherichia coli has been solved by X-ray crystallography at 2.4 A resolution. The structure is representative of a broad class of domains/proteins that regulate the conductance of K+ (here referred to as RCK domains) in prokaryotic K...


    pub_type: 杂志文章


    authors: Jiang Y,Pico A,Cadene M,Chait BT,MacKinnon R

    更新日期:2001-03-01 00:00:00

  • There and back again: the corticobulbar loop.

    abstract::Feedback is a ubiquitous anatomical feature of sensory processing in vertebrates. In this issue of Neuron, two papers (Boyd et al., 2012, and Markopoulos et al., 2012) analyze the features of feedback from olfactory cortex to olfactory bulb. ...


    pub_type: 评论,杂志文章


    authors: Oswald AM,Urban NN

    更新日期:2012-12-20 00:00:00

  • Excitatory and Inhibitory Subnetworks Are Equally Selective during Decision-Making and Emerge Simultaneously during Learning.

    abstract::Inhibitory neurons, which play a critical role in decision-making models, are often simplified as a single pool of non-selective neurons lacking connection specificity. This assumption is supported by observations in the primary visual cortex: inhibitory neurons are broadly tuned in vivo and show non-specific connecti...


    pub_type: 杂志文章


    authors: Najafi F,Elsayed GF,Cao R,Pnevmatikakis E,Latham PE,Cunningham JP,Churchland AK

    更新日期:2020-01-08 00:00:00

  • Losing the lust for life: a new role for an old feeding Peptide?

    abstract::A recent paper in Nature (Lim et al., 2012) describes the effects of melanocortin receptors in the nucleus accumbens. The studies connect a hypothalamic peptide system with brain reward centers and show effects on specific neuronal populations and behavioral components of mood. ...


    pub_type: 评论,杂志文章


    authors: Land BB,DiLeone RJ

    更新日期:2012-08-09 00:00:00

  • Neuron-specific expression of a hamster prion protein minigene in transgenic mice induces susceptibility to hamster scrapie agent.

    abstract::To study the effect of cell type-restricted hamster PrP expression on susceptibility to the hamster scrapie agent, we generated transgenic mice using a 1 kb hamster cDNA clone containing the 0.76 kb HPrP open reading frame under control of the neuron-specific enolase promoter. In these mice, expression of HPrP was det...


    pub_type: 杂志文章


    authors: Race RE,Priola SA,Bessen RA,Ernst D,Dockter J,Rall GF,Mucke L,Chesebro B,Oldstone MB

    更新日期:1995-11-01 00:00:00