scholarly journals Structure of the Shaker Kv channel and mechanism of slow C-type inactivation

2021 ◽  
Author(s):  
Xiao-Feng Tan ◽  
Chanhyung Bae ◽  
Robyn Stix ◽  
Anabel I. Fernandez ◽  
Kate Huffer ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Molecular Mechanisms ◽  
Short Term Memory ◽  
Ion Selectivity ◽  
Neuronal Firing ◽  
Ion Permeation ◽  
Short Term ◽  
Kv Channel ◽  
Kv Channels ◽  
Cryo Electron Microscopy

AbstractVoltage-activated potassium (Kv) channels open upon membrane depolarization and proceed to spontaneously inactivate. Inactivation controls neuronal firing rates and serves as a form of short-term memory, and is implicated in various human neurological disorders. Here, we use high-resolution cryo-electron microscopy and computer simulations to determine one of the molecular mechanisms underlying this physiologically crucial process. Structures of the activated Shaker Kv channel and of its W434F mutant in lipid bilayers demonstrate that C-type inactivation entails the dilation of the ion selectivity filter, and the repositioning of neighboring residues known to be functionally critical. Microsecond-scale molecular dynamics trajectories confirm these changes inhibit rapid ion permeation through the channel. This long-sought breakthrough establishes how eukaryotic K+ channels self-regulate their functional state through the plasticity of their selectivity filters.

scholarly journals Molecular Template for a Voltage Sensor in a Novel K+ Channel. III. Functional Reconstitution of a Sensorless Pore Module from a Prokaryotic Kv Channel

2008 ◽  
Vol 132 (6) ◽  
pp. 651-666 ◽  
Author(s):  
Jose S. Santos ◽  
Sergey M. Grigoriev ◽  
Mauricio Montal
Keyword(s):  
Lipid Bilayers ◽  
Single Channel ◽  
Functional Module ◽  
Ion Selectivity ◽  
Ionic Currents ◽  
K Channel ◽  
Voltage Sensing ◽  
Kv Channel ◽  
Kv Channels ◽  
Conduction Properties

KvLm is a prokaryotic voltage-gated K+ (Kv) channel from Listeria monocytogenes. The sequence of the voltage-sensing module (transmembrane segments S1-S4) of KvLm is atypical in that it contains only three of the eight conserved charged residues known to be deterministic for voltage sensing in eukaryotic Kv's. In contrast, the pore module (PM), including the S4-S5 linker and cytoplasmic tail (linker-S5-P-S6-C-terminus) of KvLm, is highly conserved. Here, the full-length (FL)-KvLm and the KvLm-PM only proteins were expressed, purified, and reconstituted into giant liposomes. The properties of the reconstituted FL-KvLm mirror well the characteristics of the heterologously expressed channel in Escherichia coli spheroplasts: a right-shifted voltage of activation, micromolar tetrabutylammonium-blocking affinity, and a single-channel conductance comparable to that of eukaryotic Kv's. Conversely, ionic currents through the PM recapitulate both the conductance and blocking properties of the FL-KvLm, yet the KvLm-PM exhibits only rudimentary voltage dependence. Given that the KvLm-PM displays many of the conduction properties of FL-KvLm and of other eukaryotic Kv's, including strict ion selectivity, we conclude that self-assembly of the PM subunits in lipid bilayers, in the absence of the voltage-sensing module, generates a conductive oligomer akin to that of the native KvLm, and that the structural independence of voltage sensing and PMs observed in eukaryotic Kv channels was initially implemented by nature in the design of prokaryotic Kv channels. Collectively, the results indicate that this robust functional module will prove valuable as a molecular template for coupling new sensors and to elucidate PM residue–specific contributions to Kv conduction properties.

scholarly journals A Temporal Activity of CA1 Neurons Underlying Short-Term Memory for Social Recognition Altered in PTEN Mouse Models of Autism Spectrum Disorder

2021 ◽  
Vol 15 ◽  
Author(s):  
An-Ping Chai ◽  
Xue-Feng Chen ◽  
Xiao-Shan Xu ◽  
Na Zhang ◽  
Meng Li ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Short Term Memory ◽  
Autism Spectrum ◽  
Social Recognition ◽  
Neuronal Firing ◽  
Spectrum Disorder ◽  
Long Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Ca1 Neurons

Memory-guided social recognition identifies someone from previous encounters or experiences, but the mechanisms of social memory remain unclear. Here, we find that a short-term memory from experiencing a stranger mouse lasting under 30 min interval is essential for subsequent social recognition in mice, but that interval prolonged to hours by replacing the stranger mouse with a familiar littermate. Optogenetic silencing of dorsal CA1 neuronal activity during trials or inter-trial intervals disrupted short-term memory-guided social recognition, without affecting the ability of being sociable or long-term memory-guided social recognition. Postnatal knockdown or knockout of autism spectrum disorder (ASD)-associated phosphatase and tensin homolog (PTEN) gene in dorsal hippocampal CA1 similarly impaired neuronal firing rate in vitro and altered firing pattern during social recognition. These PTEN mice showed deficits in social recognition with stranger mouse rather than littermate and exhibited impairment in T-maze spontaneous alternation task for testing short-term spatial memory. Thus, we suggest that a temporal activity of dorsal CA1 neurons may underlie formation of short-term memory to be critical for organizing subsequent social recognition but that is possibly disrupted in ASD.

scholarly journals Conserved His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivity

2020 ◽  
Author(s):  
Nate Yoder ◽  
Eric Gouaux
Keyword(s):  
Ion Channels ◽  
Ion Selectivity ◽  
Fear Memory ◽  
Amino Terminus ◽  
Ion Permeation ◽  
Structural Explanation ◽  
Cryo Electron Microscopy ◽  
Acid Sensing Ion Channels ◽  
And Function

ABSTRACTAcid-sensing ion channels (ASICs) are proton-gated members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout central and peripheral nervous systems. The homotrimeric splice variant ASIC1a has been implicated in nociception, fear memory, mood disorders and ischemia. Here we extract full-length chicken ASIC1a (cASIC1a) from cell membranes using styrene maleic acid (SMA) copolymer, yielding structures of ASIC1a channels in both high pH resting and low pH desensitized conformations by single-particle cryo-electron microscopy (cryo-EM). The structures of resting and desensitized channels reveal a reentrant loop at the amino terminus of ASIC1a that includes the highly conserved ‘His-Gly’ (HG) motif. The reentrant loop lines the lower ion permeation pathway and buttresses the ‘Gly-Ala-Ser’ (GAS) constriction, thus providing a structural explanation for the role of the His-Gly dipeptide in the structure and function of ASICs.

scholarly journals The His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivity

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Nate Yoder ◽  
Eric Gouaux
Keyword(s):  
Ion Channels ◽  
Ion Selectivity ◽  
Fear Memory ◽  
Amino Terminus ◽  
Ion Permeation ◽  
Structural Explanation ◽  
Cryo Electron Microscopy ◽  
Acid Sensing Ion Channels ◽  
And Function

Acid-sensing ion channels (ASICs) are proton-gated members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout the central and peripheral nervous systems. The homotrimeric splice variant ASIC1a has been implicated in nociception, fear memory, mood disorders and ischemia. Here, we extract full-length chicken ASIC1 (cASIC1) from cell membranes using styrene maleic acid (SMA) copolymer, elucidating structures of ASIC1 channels in both high pH resting and low pH desensitized conformations by single-particle cryo-electron microscopy (cryo-EM). The structures of resting and desensitized channels reveal a reentrant loop at the amino terminus of ASIC1 that includes the highly conserved ‘His-Gly’ (HG) motif. The reentrant loop lines the lower ion permeation pathway and buttresses the ‘Gly-Ala-Ser’ (GAS) constriction, thus providing a structural explanation for the role of the His-Gly dipeptide in the structure and function of ASICs.

scholarly journals Stabilization of the Conductive Conformation of a Voltage-gated K+ (Kv) Channel

2013 ◽  
Vol 288 (23) ◽  
pp. 16619-16628 ◽  
Author(s):  
Jose S. Santos ◽  
Ruhma Syeda ◽  
Mauricio Montal
Keyword(s):  
Lipid Bilayers ◽  
Lipid Membranes ◽  
Single Channel ◽  
Cysteine Residue ◽  
Covalent Attachment ◽  
Voltage Sensitivity ◽  
Voltage Gated ◽  
Kv Channel ◽  
Kv Channels ◽  
Peptide Toxin

Voltage-gated K+ (Kv) channels are molecular switches that sense membrane potential and in response open to allow K+ ions to diffuse out of the cell. In these proteins, sensor and pore belong to two distinct structural modules. We previously showed that the pore module alone is a robust yet dynamic structural unit in lipid membranes and that it senses potential and gates open to conduct K+ with unchanged fidelity. The implication is that the voltage sensitivity of K+ channels is not solely encoded in the sensor. Given that the coupling between sensor and pore remains elusive, we asked whether it is then possible to convert a pore module characterized by brief openings into a conductor with a prolonged lifetime in the open state. The strategy involves selected probes targeted to the filter gate of the channel aiming to modulate the probability of the channel being open assayed by single channel recordings from the sensorless pore module reconstituted in lipid bilayers. Here we show that the premature closing of the pore is bypassed by association of the filter gate with two novel open conformation stabilizers: an antidepressant and a peptide toxin known to act selectively on Kv channels. Such stabilization of the conductive conformation of the channel is faithfully mimicked by the covalent attachment of fluorescein at a cysteine residue selectively introduced near the filter gate. This modulation prolongs the occupancy of permeant ions at the gate. It is this longer embrace between ion and gate that we conjecture underlies the observed stabilization of the conductive conformation. This study provides a new way of thinking about gating.

Conceptual short-term memory (CSTM) supports core claims of Christiansen and Chater

2016 ◽  
Vol 39 ◽  
Author(s):  
Mary C. Potter
Keyword(s):  
Working Memory ◽  
Rapid Serial Visual Presentation ◽  
Language Comprehension ◽  
Short Term Memory ◽  
Visual Presentation ◽  
Long Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Use Of Knowledge

AbstractRapid serial visual presentation (RSVP) of words or pictured scenes provides evidence for a large-capacity conceptual short-term memory (CSTM) that momentarily provides rich associated material from long-term memory, permitting rapid chunking (Potter 1993; 2009; 2012). In perception of scenes as well as language comprehension, we make use of knowledge that briefly exceeds the supposed limits of working memory.

Working, Declarative, and Procedural Memory in Children With Developmental Language Disorder

2020 ◽  
Vol 63 (12) ◽  
pp. 4162-4178
Author(s):  
Emily Jackson ◽  
Suze Leitão ◽  
Mary Claessen ◽  
Mark Boyes
Keyword(s):  
Working Memory ◽  
Short Term Memory ◽  
Language Disorder ◽  
Declarative Memory ◽  
Memory Systems ◽  
Procedural Memory ◽  
Typically Developing ◽  
Short Term ◽  
Term Memory ◽  
Visual Spatial

Purpose Previous research into the working, declarative, and procedural memory systems in children with developmental language disorder (DLD) has yielded inconsistent results. The purpose of this research was to profile these memory systems in children with DLD and their typically developing peers. Method One hundred four 5- to 8-year-old children participated in the study. Fifty had DLD, and 54 were typically developing. Aspects of the working memory system (verbal short-term memory, verbal working memory, and visual–spatial short-term memory) were assessed using a nonword repetition test and subtests from the Working Memory Test Battery for Children. Verbal and visual–spatial declarative memory were measured using the Children's Memory Scale, and an audiovisual serial reaction time task was used to evaluate procedural memory. Results The children with DLD demonstrated significant impairments in verbal short-term and working memory, visual–spatial short-term memory, verbal declarative memory, and procedural memory. However, verbal declarative memory and procedural memory were no longer impaired after controlling for working memory and nonverbal IQ. Declarative memory for visual–spatial information was unimpaired. Conclusions These findings indicate that children with DLD have deficits in the working memory system. While verbal declarative memory and procedural memory also appear to be impaired, these deficits could largely be accounted for by working memory skills. The results have implications for our understanding of the cognitive processes underlying language impairment in the DLD population; however, further investigation of the relationships between the memory systems is required using tasks that measure learning over long-term intervals. Supplemental Material https://doi.org/10.23641/asha.13250180

Comparison of Auditory, Language, Memory, and Attention Abilities in Children With and Without Listening Difficulties

2020 ◽  
Vol 29 (4) ◽  
pp. 710-727
Author(s):  
Beula M. Magimairaj ◽  
Naveen K. Nagaraj ◽  
Alexander V. Sergeev ◽  
Natalie J. Benafield
Keyword(s):  
Auditory Processing ◽  
Short Term Memory ◽  
Group Differences ◽  
Long Term Memory ◽  
Short Term ◽  
Significant Group ◽  
Term Memory ◽  
Memory And Attention ◽  
Speed And Accuracy

Objectives School-age children with and without parent-reported listening difficulties (LiD) were compared on auditory processing, language, memory, and attention abilities. The objective was to extend what is known so far in the literature about children with LiD by using multiple measures and selective novel measures across the above areas. Design Twenty-six children who were reported by their parents as having LiD and 26 age-matched typically developing children completed clinical tests of auditory processing and multiple measures of language, attention, and memory. All children had normal-range pure-tone hearing thresholds bilaterally. Group differences were examined. Results In addition to significantly poorer speech-perception-in-noise scores, children with LiD had reduced speed and accuracy of word retrieval from long-term memory, poorer short-term memory, sentence recall, and inferencing ability. Statistically significant group differences were of moderate effect size; however, standard test scores of children with LiD were not clinically poor. No statistically significant group differences were observed in attention, working memory capacity, vocabulary, and nonverbal IQ. Conclusions Mild signal-to-noise ratio loss, as reflected by the group mean of children with LiD, supported the children's functional listening problems. In addition, children's relative weakness in select areas of language performance, short-term memory, and long-term memory lexical retrieval speed and accuracy added to previous research on evidence-based areas that need to be evaluated in children with LiD who almost always have heterogenous profiles. Importantly, the functional difficulties faced by children with LiD in relation to their test results indicated, to some extent, that commonly used assessments may not be adequately capturing the children's listening challenges. Supplemental Material https://doi.org/10.23641/asha.12808607

The Link Between Verbal Short-Term Memory and Anomia Treatment Gains

2019 ◽  
Vol 28 (3) ◽  
pp. 1039-1052
Author(s):  
Reva M. Zimmerman ◽  
JoAnn P. Silkes ◽  
Diane L. Kendall ◽  
Irene Minkina
Keyword(s):  
Short Term Memory ◽  
Controlled Trial ◽  
Treatment Success ◽  
Linear Regression Models ◽  
Language Performance ◽  
Short Term ◽  
Term Memory ◽  
Treatment Gains ◽  
Post Hoc

Purpose A significant relationship between verbal short-term memory (STM) and language performance in people with aphasia has been found across studies. However, very few studies have examined the predictive value of verbal STM in treatment outcomes. This study aims to determine if verbal STM can be used as a predictor of treatment success. Method Retrospective data from 25 people with aphasia in a larger randomized controlled trial of phonomotor treatment were analyzed. Digit and word spans from immediately pretreatment were run in multiple linear regression models to determine whether they predict magnitude of change from pre- to posttreatment and follow-up naming accuracy. Pretreatment, immediately posttreatment, and 3 months posttreatment digit and word span scores were compared to determine if they changed following a novel treatment approach. Results Verbal STM, as measured by digit and word spans, did not predict magnitude of change in naming accuracy from pre- to posttreatment nor from pretreatment to 3 months posttreatment. Furthermore, digit and word spans did not change from pre- to posttreatment or from pretreatment to 3 months posttreatment in the overall analysis. A post hoc analysis revealed that only the less impaired group showed significant changes in word span scores from pretreatment to 3 months posttreatment. Discussion The results suggest that digit and word spans do not predict treatment gains. In a less severe subsample of participants, digit and word span scores can change following phonomotor treatment; however, the overall results suggest that span scores may not change significantly. The implications of these findings are discussed within the broader purview of theoretical and empirical associations between aphasic language and verbal STM processing.

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