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TRPC6-mediated ERK1/2 Activation Regulates Neuronal Excitability via Subcellular Kv4.3 Localization in the Rat Hippocampus

Overview of attention for article published in Frontiers in Cellular Neuroscience, December 2017
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Title
TRPC6-mediated ERK1/2 Activation Regulates Neuronal Excitability via Subcellular Kv4.3 Localization in the Rat Hippocampus
Published in
Frontiers in Cellular Neuroscience, December 2017
DOI 10.3389/fncel.2017.00413
Pubmed ID
Authors

Ji-Eun Kim, Jin-Young Park, Tae-Cheon Kang

Abstract

Recently, we have reported that transient receptor potential channel-6 (TRPC6) plays an important role in the regulation of neuronal excitability and synchronization of spiking activity in the dentate granule cells (DGC). However, the underlying mechanisms of TRPC6 in these phenomena have been still unclear. In the present study, we investigated the role of TRPC6 in subcellular localization of Kv4.3 and its relevance to neuronal excitability in the rat hippocampus. TRPC6 knockdown increased excitability and inhibitory transmission in the DGC and the CA1 neurons in response to a paired-pulse stimulus. However, TRPC6 knockdown impaired γ-aminobutyric acid (GABA)ergic inhibition in the hippocampus during and after high-frequency stimulation (HFS). TRPC6 knockdown reduced the Kv4.3 clusters in membrane fractions and its dendritic localization on DGC and GABAergic interneurons. TRPC6 knockdown also decreased extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and the efficacy of 4-aminopyridine (4-AP) in neuronal excitability. An ERK1/2 inhibitor generated multiple population spikes in response to a paired-pulse stimulus, concomitant with reduced membrane Kv4.3 translocation. A TRPC6 activator (hyperforin) reversed the effects of TRPC knockdown, except paired-pulse inhibition. These findings provide valuable clues indicating that TRPC6-mediated ERK1/2 activation may regulate subcellular Kv4.3 localization in DGC and interneurons, which is cause-effect relationship between neuronal excitability and seizure susceptibility.

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The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 15 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 4 27%
Student > Ph. D. Student 2 13%
Other 1 7%
Professor 1 7%
Student > Doctoral Student 1 7%
Other 2 13%
Unknown 4 27%
Readers by discipline Count As %
Neuroscience 3 20%
Biochemistry, Genetics and Molecular Biology 2 13%
Energy 1 7%
Agricultural and Biological Sciences 1 7%
Medicine and Dentistry 1 7%
Other 1 7%
Unknown 6 40%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 January 2018.
All research outputs
#15,696,101
of 25,311,095 outputs
Outputs from Frontiers in Cellular Neuroscience
#2,272
of 4,684 outputs
Outputs of similar age
#246,434
of 454,126 outputs
Outputs of similar age from Frontiers in Cellular Neuroscience
#43
of 104 outputs
Altmetric has tracked 25,311,095 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,684 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one is in the 48th percentile – i.e., 48% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 454,126 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 104 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.