Physiological roles of Kv2 channels in entorhinal cortex layer II stellate cells revealed by Guangxitoxin‐1E

Hönigsperger, Christoph; Nigro, Maximiliano José; Storm, Johan F.

doi:10.1113/jp273024

Cited by 22 publications

(20 citation statements)

References 69 publications

(214 reference statements)

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“…Liu and Bean (2014) observed modest spike broadening in CA1 pyramidal cells with GxTx. Honigsperger et al (2013) also observed that GxTx blocked I K but slowed AP repolarization only after the first AP during repetitive firing in ERC stellate cells (layer 2). Both CA1 pyramidal cells and ERC pyramidal cells typically have broader APs than neocortical pyramidal cells, which may allow for the relatively kinetically slow K v 2 channels to contribute to repolarization.…”

Section: Discussionmentioning

confidence: 81%

Roles of specific K_v channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex

Pathak

Guan

Foehring

2016

Journal of Neurophysiology

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The action potential (AP) is a fundamental feature of excitable cells that serves as the basis for long-distance signaling in the nervous system. There is considerable diversity in the appearance of APs and the underlying repolarization mechanisms in different neuronal types (reviewed in Bean BP. Nat Rev Neurosci 8: 451-465, 2007), including among pyramidal cell subtypes. In the present work, we used specific pharmacological blockers to test for contributions of Kv1, Kv2, or Kv4 channels to repolarization of single APs in two genetically defined subpopulations of pyramidal cells in layer 5 of mouse somatosensory cortex (etv1 and glt) as well as pyramidal cells from layer 2/3. These three subtypes differ in AP properties (Groh A, Meyer HS, Schmidt EF, Heintz N, Sakmann B, Krieger P. Cereb Cortex 20: 826-836, 2010; Guan D, Armstrong WE, Foehring RC. J Neurophysiol 113: 2014-2032, 2015) as well as laminar position, morphology, and projection targets. We asked what the roles of Kv1, Kv2, and Kv4 channels are in AP repolarization and whether the underlying mechanisms are pyramidal cell subtype dependent. We found that Kv4 channels are critically involved in repolarizing neocortical pyramidal cells. There are also pyramidal cell subtype-specific differences in the role for Kv1 channels. Only Kv4 channels were involved in repolarizing the narrow APs of glt cells. In contrast, in etv1 cells and layer 2/3 cells, the broader APs are partially repolarized by Kv1 channels in addition to Kv4 channels. Consistent with their activation in the subthreshold range, Kv1 channels also regulate AP voltage threshold in all pyramidal cell subtypes.

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Section: Discussionmentioning

confidence: 81%

Roles of specific K_v channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex

Pathak

Guan

Foehring

2016

Journal of Neurophysiology

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“…Based on this correlation, we would expect that decreasing K v 2.1 functional expression should increase AHP amp values. However, convergent genetic and pharmacological evidence suggests the opposite: decreasing K v 2.1 activity or expression decreases AHP amp values [ 45 , 46 ]. Delving deeper, the Kcnb1- AHP amp correlation appears driven in part by gross differences between excitatory and non-excitatory cell types, with excitatory cells strongly expressing Kcnb1 and also having small AHP amp relative to non-excitatory cell types ( S5C Fig ).…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic correlates of neuron electrophysiological diversity

Tripathy

Toker

et al. 2017

PLoS Comput Biol

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How neuronal diversity emerges from complex patterns of gene expression remains poorly understood. Here we present an approach to understand electrophysiological diversity through gene expression by integrating pooled- and single-cell transcriptomics with intracellular electrophysiology. Using neuroinformatics methods, we compiled a brain-wide dataset of 34 neuron types with paired gene expression and intrinsic electrophysiological features from publically accessible sources, the largest such collection to date. We identified 420 genes whose expression levels significantly correlated with variability in one or more of 11 physiological parameters. We next trained statistical models to infer cellular features from multivariate gene expression patterns. Such models were predictive of gene-electrophysiological relationships in an independent collection of 12 visual cortex cell types from the Allen Institute, suggesting that these correlations might reflect general principles relating expression patterns to phenotypic diversity across very different cell types. Many associations reported here have the potential to provide new insights into how neurons generate functional diversity, and correlations of ion channel genes like Gabrd and Scn1a (Nav1.1) with resting potential and spiking frequency are consistent with known causal mechanisms. Our work highlights the promise and inherent challenges in using cell type-specific transcriptomics to understand the mechanistic origins of neuronal diversity.

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“…Based on this correlation, we would expect that decreasing K v 2.1 functional expression should increase AHP amp values. However, convergent genetic and pharmacological evidence suggests the opposite: decreasing K v 2.1 activity or expression decreases AHP amp values 42,43 . Delving deeper, the Kcnb1-AHP amp correlation appears driven in part by gross differences between excitatory and non-excitatory cell types, with excitatory cells strongly expressing Kcnb1 and also having small AHP amp relative to non-excitatory cell types (Supplemental Figure 4C).…”

Section: Causal Relationships Between Discovered Gene-electrophysiolomentioning

confidence: 99%

Transcriptomic correlates of neuron electrophysiological diversity

Tripathy

Toker

et al. 2017

Preprint

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How neuronal diversity emerges from complex patterns of gene expression remains poorly understood. Here we present an approach to understand electrophysiological diversity through gene expression by integrating transcriptomics with intracellular electrophysiology. Using a brain-wide dataset of 34 neuron types, we identified 420 genes whose expression levels significantly correlated with variability in one or more of 11 electrophysiological parameters. The majority of these correlations were consistent in an independent sample of 12 visual cortex cell types. Many associations reported here have the potential to provide new insights into how neurons generate functional diversity, and correlations of ion channel genes like Gabrd and Scn1a (Nav1.1) with resting potential and spiking frequency are consistent with known causal mechanisms. These results suggest that despite the complexity linking gene expression to electrophysiology, there are likely some general principles that govern how individual genes establish phenotypic diversity across very different cell types.

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Physiological roles of Kv2 channels in entorhinal cortex layer II stellate cells revealed by Guangxitoxin‐1E

Cited by 22 publications

References 69 publications

Roles of specific K_v channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex

Roles of specific K_v channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex

Transcriptomic correlates of neuron electrophysiological diversity

Transcriptomic correlates of neuron electrophysiological diversity

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Physiological roles of Kv2 channels in entorhinal cortex layer II stellate cells revealed by Guangxitoxin‐1E

Cited by 22 publications

References 69 publications

Roles of specific Kv channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex

Roles of specific Kv channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex

Transcriptomic correlates of neuron electrophysiological diversity

Transcriptomic correlates of neuron electrophysiological diversity

Contact Info

Product

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Roles of specific K_v channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex

Roles of specific K_v channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex