Neuroscience_topics
Follow
Find
16.8K views | +5 today
Scooped by Julien Hering, PhD
onto Neuroscience_topics
Scoop.it!

Brain excitability and connectivity of neuronal assemblies in Alzheimer's disease: From animal models to human findings

Brain excitability and connectivity of neuronal assemblies in Alzheimer's disease: From animal models to human findings | Neuroscience_topics | Scoop.it

[Review] The human brain contains about 100 billion neurons forming an intricate network of innumerable connections, which continuously adapt and rewire themselves following inputs from external and internal environments as well as the physiological synaptic, dendritic and axonal sculpture during brain maturation and throughout the life span.

Growing evidence supports the idea that Alzheimer's disease (AD) targets selected and functionally connected neuronal networks and, specifically, their synaptic terminals, affecting brain connectivity well before producing neuronal loss and compartmental atrophy.

The understanding of the molecular mechanisms underlying the dismantling of neuronal circuits and the implementation of ‘clinically oriented’ methods to map-out the dynamic interactions amongst neuronal assemblies will enhance early/pre-symptomatic diagnosis and monitoring of disease progression. More important, this will open the avenues to innovative treatments, bridging the gap between molecular mechanisms and the variety of symptoms forming disease phenotype.

In the present review a set of evidence supports the idea that altered brain connectivity, exhausted neural plasticity and aberrant neuronal activity are facets of the same coin linked to age-related neurodegenerative dementia of Alzheimer type.

Investigating their respective roles in AD pathophysiology will help in translating findings from basic research to clinical applications. (...) - By D'Amelio M & Rossini PMProgress in Neurobiology, Volume 99, Issue 1, October 2012, Pages 42–60

more...
No comment yet.
Neuroscience_topics
Neuroscience: CNS disease, pain, brain research, ion channels, synaptic transmission, channelopathies, neuronal network
Your new post is loading...
Your new post is loading...
Scooped by Julien Hering, PhD
Scoop.it!

Autaptic self-inhibition of cortical GABAergic neurons: Synaptic narcissism or useful introspection?

Autaptic self-inhibition of cortical GABAergic neurons: Synaptic narcissism or useful introspection? | Neuroscience_topics | Scoop.it
Highlights: 

-  Specific connectivity patterns between interneurons and excitatory cells.

- Cortical disinhibition is necessary for behavioral functions.

- Cortical disinhibition is provided by specific interneuron–interneuron connections.

- Autaptic self-inhibition of PV cells: a very efficient disinhibition stratagem.

- A dual role of autaptic inhibition in temporally coordinating PV basket cells. (...) - by Deleuze C et al., Current Opinion in Neurobiology, Volume 26, June 2014, Pages 64–71

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Neuronal Voltage-Gated Calcium Channels: Structure, Function, and Dysfunction

Neuronal Voltage-Gated Calcium Channels: Structure, Function, and Dysfunction | Neuroscience_topics | Scoop.it

[Review] Voltage-gated calcium channels are the primary mediators of depolarization-induced calcium entry into neurons. There is great diversity of calcium channel subtypes due to multiple genes that encode calcium channel α1 subunits, coassembly with a variety of ancillary calcium channel subunits, and alternative splicing. This allows these channels to fulfill highly specialized roles in specific neuronal subtypes and at particular subcellular loci. While calcium channels are of critical importance to brain function, their inappropriate expression or dysfunction gives rise to a variety of neurological disorders, including, pain, epilepsy, migraine, and ataxia. This Review discusses salient aspects of voltage-gated calcium channel function, physiology, and pathophysiology. - by Simms BA & Zamponi GW, Neuron, Volume 82, Issue 1, p24–45, 2 April 2014

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Biomarkers could predict Alzheimer's before it starts

Biomarkers could predict Alzheimer's before it starts | Neuroscience_topics | Scoop.it

Study identifies potential blood test for cognitive decline.

A simple blood test has the potential to predict whether a healthy person will develop symptoms of dementia within two or three years. If larger studies uphold the results, the test could fill a major gap in strategies to combat brain degeneration, which is thought to show symptoms only at a stage when it too late to treat effectively. (...) - by Alison Abbott, Nature, 09 March 2014

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Kv7 channels as targets for anti-epileptic and psychiatric drug-development

Kv7 channels as targets for anti-epileptic and psychiatric drug-development | Neuroscience_topics | Scoop.it
The Kv7 channels, a family of voltage-dependent K+ channels (Kv7.1–Kv7.5), have gained much attention in drug discovery especially because four members are genetically linked to diseases. For disorders of the CNS focus was originally on epilepsy and pain, but it is becoming increasingly evident that Kv7 channels can also be valid targets for psychiatric disorders, such as anxiety and mania. The common denominator is probably neuronal hyperexcitability in different brain areas, which can be successfully attenuated by pharmacological increment of Kv7 channel activity. This perspective attempts to review the current status and challenges for CNS drug discovery based on Kv7 channels as targets for neurological and psychiatric indications with special focus on selectivity and mode-of-actions. - by Grunnet M. et al., European Journal of Pharmacology, Volume 726, 5 March 2014, Pages 133–137
more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Inhibitory Plasticity Dictates the Sign of Plasticity at Excitatory Synapses

The broad connectivity of inhibitory interneurons and the capacity of inhibitory synapses to be plastic make them ideal regulators of the level of excitability of many neurons simultaneously. Whether inhibitory synaptic plasticity may also contribute to the selective regulation of single neurons and local microcircuits activity has not been investigated. Here we demonstrate that in rat primary visual cortex inhibitory synaptic plasticity is connection specific and depends on the activation of postsynaptic GABAB–Gi/o protein signaling. Through the activation of this intracellular signaling pathway, inhibitory plasticity can alter the state of a single postsynaptic neuron and directly affect the induction of plasticity at its glutamatergic inputs. This interaction is modulated by sensory experience. Our data demonstrate that in recurrent circuits, excitatory and inhibitory forms of synaptic plasticity are not integrated as independent events, but interact to cooperatively drive the activity-dependent rewiring of local microcircuits. (...) - by Wang L and Maffei A, The Journal of Neuroscience, 22 January 2014, 34(4): 1083-1093

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Structural basis for Ca2+ selectivity of a voltage-gated calcium channel

Structural basis for Ca2+ selectivity of a voltage-gated calcium channel | Neuroscience_topics | Scoop.it

Voltage-gated calcium (CaV) channels catalyse rapid, highly selective influx of Ca2+ into cells despite a 70-fold higher extracellular concentration of Na+. How CaV channels solve this fundamental biophysical problem remains unclear. Here we report physiological and crystallographic analyses of a calcium selectivity filter constructed in the homotetrameric bacterial NaV channel NaVAb. Our results reveal interactions of hydrated Ca2+ with two high-affinity Ca2+-binding sites followed by a third lower-affinity site that would coordinate Ca2+ as it moves inward. At the selectivity filter entry, Site 1 is formed by four carboxyl side chains, which have a critical role in determining Ca2+ selectivity. Four carboxyls plus four backbone carbonyls form Site 2, which is targeted by the blocking cations Cd2+ and Mn2+, with single occupancy. The lower-affinity Site 3 is formed by four backbone carbonyls alone, which mediate exit into the central cavity. This pore architecture suggests a conduction pathway involving transitions between two main states with one or two hydrated Ca2+ ions bound in the selectivity filter and supports a ‘knock-off’ mechanism of ion permeation through a stepwise-binding process. The multi-ion selectivity filter of our CaVAb model establishes a structural framework for understanding the mechanisms of ion selectivity and conductance by vertebrate CaV channels. (...) - by Tang et al.Nature 505, 56–61 (02 January 2014)

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Modulation of NMDA receptor at the synapse: Promising therapeutic interventions in disorders of the nervous system

Modulation of NMDA receptor at the synapse: Promising therapeutic interventions in disorders of the nervous system | Neuroscience_topics | Scoop.it

[Review] There is general agreement that excessive activation of N-methyl-D-aspartate (NMDA) receptors plays a key role in mediating at least some aspects of synaptic dysfunction in several central nervous system disorders. On this view, in the last decades, research focused on the discovery of different compounds able to reduce NMDA receptor activity, such as classical and/or subunit-specific antagonists. However, the increasing body of knowledge on specific signaling pathways downstream NMDA receptors led to the identification of new pharmacological targets for NMDA receptor-related pathological conditions. Moreover, besides over-activation, several studies indicated that also abnormal NMDA receptor trafficking, resulting in the modification of the receptor subunit composition at the synapse, has a major role in the pathogenesis of several brain disorders. For this reason, the discovery of the molecular mechanisms regulating the abundance of synaptic versus extra-synaptic NMDA receptors as well as the activation of the specific signaling pathways downstream the different NMDA receptor subtypes is needed for the development of novel therapeutic approaches for NMDA receptor-dependent synaptic dysfunction. (...) - Mellone M. & Gardoni FEuropean Journal of Pharmacology

Volume 719, Issues 1–3, 5 November 2013, Pages 75–83

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Choosing an animal model for the study of Huntington's disease

Since the identification of the causative gene in Huntington's disease (HD), a number of animal models of this disorder have been developed. A frequently asked question is: which of these models most closely recapitulates the human disease? In this Review, we provide an overview of the currently available animal models of HD in the context of the clinical features of the disease. In doing so, we highlight their strengths and limitations for modelling specific symptoms of the disease. This should highlight the animal model that is best suited to address a particular question of interest and, ultimately, to expedite the discovery of treatments that will prevent or slow the progression of HD. - by Pouladi MA et al.Nature Reviews Neuroscience 14, 708–721 (2013) 

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Neuroscience thinks big (and collaboratively)

Despite cash-strapped times for research, several ambitious collaborative neuroscience projects have attracted large amounts of funding and media attention. In Europe, the Human Brain Project aims to develop a large-scale computer simulation of the brain, whereas in the United States, the Brain Activity Map is working towards establishing a functional connectome of the entire brain, and the Allen Institute for Brain Science has embarked upon a 10-year project to understand the mouse visual cortex (the MindScope project). US President Barack Obama's announcement of the BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies Initiative) in April 2013 highlights the political commitment to neuroscience and is expected to further foster interdisciplinary collaborations, accelerate the development of new technologies and thus fuel much needed medical advances. In this Viewpoint article, five prominent neuroscientists explain the aims of the projects and how they are addressing some of the questions (and criticisms) that have arisen. - by Kandel ER et al.Nature Reviews Neuroscience 14, 659–664 (2013) 

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Water molecules control inactivation and recovery of potassium channels

Water molecules control inactivation and recovery of potassium channels | Neuroscience_topics | Scoop.it

Just 12 molecules of water cause the long post-activation recovery period required by potassium ion channels before they can function again. Using molecular simulations that modeled a potassium channel and its immediate cellular environment, atom for atom, University of Chicago scientists have revealed this new mechanism in the function of a nearly universal biological structure, with implications ranging from fundamental biology to the design of pharmaceuticals. (...) - ScienceDaily, July 28, 2013

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Acid-sensing ion channels in pain and disease

Acid-sensing ion channels in pain and disease | Neuroscience_topics | Scoop.it

Why do neurons sense extracellular acid? In large part, this question has driven increasing investigation on acid-sensing ion channels (ASICs) in the CNS and the peripheral nervous system for the past two decades. Significant progress has been made in understanding the structure and function of ASICs at the molecular level. Studies aimed at clarifying their physiological importance have suggested roles for ASICs in pain, neurological and psychiatric disease. This Review highlights recent findings linking these channels to physiology and disease. In addition, it discusses some of the implications for therapy and points out questions that remain unanswered. (...) - by Wemmie JA et al., Nature Reviews Neuroscience 14, 461–471 (2013)

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease

NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease | Neuroscience_topics | Scoop.it

NMDA receptors (NMDARs) are glutamate-gated ion channels and are crucial for neuronal communication. NMDARs form tetrameric complexes that consist of several homologous subunits. The subunit composition of NMDARs is plastic, resulting in a large number of receptor subtypes. As each receptor subtype has distinct biophysical, pharmacological and signalling properties, there is great interest in determining whether individual subtypes carry out specific functions in the CNS in both normal and pathological conditions. Here, we review the effects of subunit composition on NMDAR properties, synaptic plasticity and cellular mechanisms implicated in neuropsychiatric disorders. Understanding the rules and roles of NMDAR diversity could provide new therapeutic strategies against dysfunctions of glutamatergic transmission - by Pierre PaolettiCamilla Bellone Qiang Zhou, Nature Reviews Neuroscience 14, 383–400 (2013)

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Where no synapses go: gatekeepers of circuit remodeling and synaptic strength

Where no synapses go: gatekeepers of circuit remodeling and synaptic strength | Neuroscience_topics | Scoop.it

Growth inhibitory molecules in the adult mammalian central nervous system (CNS) have been implicated in the blocking of axonal sprouting and regeneration following injury. Prominent CNS regeneration inhibitors include Nogo-A, oligodendrocyte myelin glycoprotein (OMgp), and chondroitin sulfate proteoglycans (CSPGs), and a key question concerns their physiological role in the naïve CNS. Emerging evidence suggests novel functions in dendrites and at synapses of glutamatergic neurons. CNS regeneration inhibitors target the neuronal actin cytoskeleton to regulate dendritic spine maturation, long-term synapse stability, and Hebbian forms of synaptic plasticity. This is accomplished in part by antagonizing plasticity-promoting signaling pathways activated by neurotrophic factors. Altered function of CNS regeneration inhibitors is associated with mental illness and loss of long-lasting memory, suggesting unexpected and novel physiological roles for these molecules in brain health. - by Mironova Y & Giger RJ, Trends in NeurosciencesVolume 36, Issue 6, June 2013, Pages 363–373

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

GABA actions and ionic plasticity in epilepsy

GABA actions and ionic plasticity in epilepsy | Neuroscience_topics | Scoop.it
[Review] Highlights:- Ionic plasticity of GABA signaling relies on short-term and long term changes in EGABA-  Cl− transport and carboanhydrases play a key role in ionic plasticity and epilepsy.

- GABAergic transmission has both seizure-suppressing and seizure-promoting effects.

- TrkB and calpain act on GABA signaling to coordinate the process of epileptogenesis.

- GABA signaling has context-specific and age-specific effects in health and disease.

- by Kaila Kai et al., Current Opinion in Neurobiology, Volume 26, June 2014, Pages 34–41

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Brain-mapping projects to join forces

Brain-mapping projects to join forces | Neuroscience_topics | Scoop.it

US and European research programmes will begin coordinating research.

 

It seems a natural pairing, almost like the hemispheres of a human brain: two controversial and ambitious projects that seek to decipher the body's control center are poised to join forces.

The European Union’s €1-billion (US$1.3-billion) Human Brain Project (HBP) and the United States’ $1-billion Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative will launch a collaboration later this year, according to government officials involved in both projects.(...) - by Sara Reardon, Nature, 18 March 2014

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

[Review] Opening paths to novel analgesics: the role of potassium channels in chronic pain

[Review] Opening paths to novel analgesics: the role of potassium channels in chronic pain | Neuroscience_topics | Scoop.it
Highlights- Potassium (K+) channels are crucial determinants of neuronal excitability.- Nerve injury or inflammation alters K+ channel activity in neurons of the pain pathway.- These changes can render neurons hyperexcitable and cause chronic pain.- Therapies targeting K+ channels may provide improved pain relief in these states. (...) - By Tsantoulas C & McMahon SB, Trends in Neurosciences, Volume 37, Issue 3, March 2014, Pages 146–158
Julien Hering, PhD's insight:

The exceptional abundance and breadth of function encountered in K+ channels has complicated efforts to untangle explicit roles in pain syndromes. Owing to advances in molecular, biochemical, electrophysiological, and genetic methods, however, we can now appreciate the involvement of specific subunits in maladaptive pain signaling after injury or inflammation. Nevertheless, there are many potential avenues of K+ involvement that have hardly been explored. It seems likely that unknown mutations in K+channel genes might contribute to inherited pain syndromes. There are many ‘silent’ K+ channel subunits for which we have little idea of whether and how they might affect pain processing. Auxiliary subunits can provide alternative substrates for pharmacological modulation; however, our understanding of these interactions in the PNS is also limited. In many chronic pain models an extensive dysregulation of several K+channels is seen, and it is unknown whether a common epigenetic control exists.

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Gephyrin: a master regulator of neuronal function : Nature Reviews Neuroscience

Gephyrin: a master regulator of neuronal function : Nature Reviews Neuroscience | Neuroscience_topics | Scoop.it

[Review] The neurotransmitters GABA and glycine mediate fast synaptic inhibition by activating ligand-gated chloride channels — namely, type A GABA (GABAA) and glycine receptors. Both types of receptors are anchored postsynaptically by gephyrin, which self-assembles into a scaffold and interacts with the cytoskeleton. Current research indicates that postsynaptic gephyrin clusters are dynamic assemblies that are held together and regulated by multiple protein–protein interactions. Moreover, post-translational modifications of gephyrin regulate the formation and plasticity of GABAergic synapses by altering the clustering properties of postsynaptic scaffolds and thereby the availability and function of receptors and other signalling molecules. Here, we discuss the formation and regulation of the gephyrin scaffold, its role in GABAergic and glycinergic synaptic function and the implications for the pathophysiology of brain disorders caused by abnormal inhibitory neurotransmission. - by Tyagarajan SK & Fritschy JM, Nature Reviews Neuroscience 15, 141–156 (2014)

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Therapeutic potential of NaV1.1 activators

Highlights:- NaV1.1 is the major sodium current in specific inhibitory interneurons.- Interneuronal dysfunction is linked to epilepsies, schizophrenia, and AD.- NaV1.1 plays a modest role in excitatory neurons.- Selective NaV1.1 activators may hold great potential as a novel treatment paradigm.

By Jensen HS et al.,  Trends in Pharmacological Sciences, Volume 35, Issue 3, p113–118, March 2014

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Neurophysiology of HCN channels: From cellular functions to multiple regulations

Neurophysiology of HCN channels: From cellular functions to multiple regulations | Neuroscience_topics | Scoop.it
Highlights
  • Hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels are involved in multiple physiological processes.
  • HCN channels are excellent targets of various cellular signals to finely regulate neuronal responses to external stimuli.
  • Dysregulation of HCN channels is involved in a variety of neurological disorders.
by He C et al.Progress in NeurobiologyVolume 112, January 2014, Pages 1–23
Julien Hering, PhD's insight:

An interesting review about HCN these must-known ion channels that are involved in numerous physiological processes and brain diseases.

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Ca2+ channel nanodomains boost local Ca2+ amplitude

Local Ca2+ signals drive important events like synaptic transmission, neural plasticity, and cardiac contraction, yet the fundamental relationship between flux through a single channel and the Ca2+amplitude within nanometers of the channel pore has eluded direct experimental measure. Here we reverse-engineer the problem by using Ca2+-dependent inactivation of channels as a nanometer-range biosensor of Ca2+ amplitude. We discovered an unexpected and dramatic boost in nanodomain Ca2+ amplitude, ten-fold higher than predicted on theoretical grounds. This boost in local Ca2+ signaling may act to maximize the biochemical information capacity of electrically\x{2011}active cells. - by Tadross MR, PNASvol. 110 no. 39, 1579415799


more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

A golden approach to ion channel inhibition

A golden approach to ion channel inhibition | Neuroscience_topics | Scoop.it

Drugs are often used in combination and, for pharmacologists, the manner of their interactions can cast light on drug mechanisms and biological processes. Here we provide simplified descriptions of commonly used analytical methods for analysing drug combinations and describe a new and practical experimental solution to address the mechanistic question: Do two channel-blocking drugs bind at the same site? We define two simple mathematical models that describe the effects of two channel blockers acting simultaneously at either the same (Syntopic Model) or different (Allotopic Model) binding sites within a channel pore. We find that the optimum concentrations of two drugs for distinguishing between the two models are related to the mathematical Golden Ratio. - by Jarvis GE & Thompson AJTrends in Pharmacological SciencesVolume 34, Issue 9, 481-488, 23 August 2013

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Control of neuronal voltage-gated calcium ion channels from RNA to protein

[Review] Highlights:
  • How many different voltage-gated calcium (CaV) channels are there and should one care?
  • All mammalian Cacna1 genes have the potential to generate hundreds of CaV channels.
  • Cell specific mechanisms control CaV channel function at RNA and protein levels according to cell type.
  • Cell specific protein–protein interactions control subcellular CaV channel trafficking and function.
  • Cell specific and subcellular expression patterns of CaV isoforms are important for disease and treatment development.

(...) - by Lipscombe D et al., Trends in Neurosciences, available online 30 July 2013

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Very long-term memories may be stored in the pattern of holes in the perineuronal net

Very long-term memories may be stored in the pattern of holes in the perineuronal net | Neuroscience_topics | Scoop.it

A hypothesis and the experiments to test it propose that very long-term memories, such as fear conditioning, are stored as the pattern of holes in the perineuronal net (PNN), a specialized ECM that envelops mature neurons and restricts synapse formation. The 3D intertwining of PNN and synapses would be imaged by serial-section EM. Lifetimes of PNN vs. intrasynaptic components would be compared with pulse-chase 15N labeling in mice and 14C content in human cadaver brains. Genetically encoded indicators and antineoepitope antibodies should improve spatial and temporal resolution of the in vivo activity of proteases that locally erode PNN. Further techniques suggested include genetic KOs, better pharmacological inhibitors, and a genetically encoded snapshot reporter, which will capture the pattern of activity throughout a large ensemble of neurons at a time precisely defined by the triggering illumination, drive expression of effector genes to mark those cells, and allow selective excitation, inhibition, or ablation to test their functional importance. The snapshot reporter should enable more precise inhibition or potentiation of PNN erosion to compare with behavioral consequences. Finally, biosynthesis of PNN components and proteases would be imaged. (...) - By Roger Y. TsienPNAS July 23, 2013 vol. 110 no. 3012456-12461

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

The Mechanism of Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels Based on Molecular Dynamics Simulation

The Mechanism of Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels Based on Molecular Dynamics Simulation | Neuroscience_topics | Scoop.it

Voltage-gated sodium (Nav) channels and their Na+/K+ selectivity are of great importance in the mammalian neuronal signaling. According to mutational analysis, the Na+/K+ selectivity in mammalian Nav channels is mainly determined by the Lys and Asp/Glu residues located at the constriction site within the selectivity filter. Despite successful molecular dynamics simulations conducted on the prokaryotic Nav channels, the lack of Lys at the constriction site of prokaryotic Nav channels limits how much can be learned about the Na+/K+selectivity in mammalian Nav channels. In this work, we modeled the mammalian Nav channel by mutating the key residues at the constriction site in a prokaryotic Nav channel (NavRh) to its mammalian counterpart. By simulating the mutant structure, we found that the Na+ preference in mammalian Nav channels is collaboratively achieved by the deselection from Lys and the selection from Asp/Glu within the constriction site. - by XIA M et al., Biophysical JournalVolume 104, Issue 11, 4 June 2013, Pages 2401–2409

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

[Review] Neurotransmitter Transporters: Structure Meets Function

[Review] Neurotransmitter Transporters: Structure Meets Function | Neuroscience_topics | Scoop.it
Highlights
  • Review of sodium coupling and conformational change in neurotransmitter transporter
  • Side-by-side structural comparison of transporter homologs GltPh and LeuT
  • Relating crystal structures of GltPh and LeuT to functional data and simulations
  • Structural and functional implications of sodium coupling in these transporters

(...) - by Focke PJ et al.StructureVolume 21, Issue 5, 694-705, 7 May 2013

more...
No comment yet.