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Arylbenzazepines Are Potent Modulators for the Delayed Rectifier K+ Channel: A Potential Mechanism for Their Neuroprotective Effects

Overview of attention for article published in PLOS ONE, June 2009
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Title
Arylbenzazepines Are Potent Modulators for the Delayed Rectifier K+ Channel: A Potential Mechanism for Their Neuroprotective Effects
Published in
PLOS ONE, June 2009
DOI 10.1371/journal.pone.0005811
Pubmed ID
Authors

Xue-Qin Chen, Jing Zhang, John L. Neumeyer, Guo-Zhang Jin, Guo-Yuan Hu, Ao Zhang, Xuechu Zhen

Abstract

(+/-) SKF83959, like many other arylbenzazepines, elicits powerful neuroprotection in vitro and in vivo. The neuroprotective action of the compound was found to partially depend on its D(1)-like dopamine receptor agonistic activity. The precise mechanism for the (+/-) SKF83959-mediated neuroprotection remains elusive. We report here that (+/-) SKF83959 is a potent blocker for delayed rectifier K(+) channel. (+/-) SKF83959 inhibited the delayed rectifier K(+) current (I(K)) dose-dependently in rat hippocampal neurons. The IC(50) value for inhibition of I(K) was 41.9+/-2.3 microM (Hill coefficient = 1.81+/-0.13, n = 6), whereas that for inhibition of I(A) was 307.9+/-38.5 microM (Hill coefficient = 1.37+/-0.08, n = 6). Thus, (+/-) SKF83959 is 7.3-fold more potent in suppressing I(K) than I(A). Moreover, the inhibition of I(K) by (+/-) SKF83959 was voltage-dependent and not related to dopamine receptors. The rapidly onset of inhibition and recovery suggests that the inhibition resulted from a direct interaction of (+/-) SKF83959 with the K(+) channel. The intracellular application of (+/-) SKF83959 had no effects of on I(K), indicating that the compound most likely acts at the outer mouth of the pore of K(+) channel. We also tested the enantiomers of (+/-) SKF83959, R-(+) SKF83959 (MCL-201), and S-(-) SKF83959 (MCL-202), as well as SKF38393; all these compounds inhibited I(K). However, (+/-) SKF83959, at either 0.1 or 1 mM, exhibited the strongest inhibition on the currents among all tested drug. The present findings not only revealed a new potent blocker of I(K) , but also provided a novel mechanism for the neuroprotective action of arylbenzazepines such as (+/-) SKF83959.

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 %
Germany 1 7%
Unknown 14 93%

Demographic breakdown

Readers by professional status Count As %
Professor 3 20%
Student > Ph. D. Student 2 13%
Researcher 2 13%
Student > Master 1 7%
Other 1 7%
Other 2 13%
Unknown 4 27%
Readers by discipline Count As %
Chemistry 3 20%
Medicine and Dentistry 2 13%
Agricultural and Biological Sciences 1 7%
Arts and Humanities 1 7%
Neuroscience 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 3. 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 28 June 2012.
All research outputs
#7,454,427
of 22,789,566 outputs
Outputs from PLOS ONE
#88,766
of 194,532 outputs
Outputs of similar age
#38,243
of 113,722 outputs
Outputs of similar age from PLOS ONE
#259
of 515 outputs
Altmetric has tracked 22,789,566 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 194,532 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.1. This one is in the 49th percentile – i.e., 49% 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 113,722 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 515 others from the same source and published within six weeks on either side of this one. This one is in the 19th percentile – i.e., 19% of its contemporaries scored the same or lower than it.