Polyunsaturated fatty acid (PUFA) analogs represent a new class of potential anti-arrhythmic KV7.1 and KV7.1+KCNE1 channel activators. In this study, we describe dual independent activating effects of negatively charged PUFA analogs on KV7.1 and KV7.1+KCNE1 that are dependent on discrete channel motifs. PUFA analogs are critically dependent on K326 in S6 of KV7.1 to increase the maximum conductance and critically dependent on specific S4 arginines in KV7.1 to shift the voltage dependence of channel opening toward negative voltages. Our findings provide insights into how KV7.1+KCNE1 activators may interact electrostatically both with the pore domain and the voltage-sensing domain to augment channel activity. We believe that the molecular understanding of how PUFA analogs induce dual independent activating effects is an important step toward the development of effective anti-arrhythmic drugs that target KV7.1 channels.
Pharmacology, Toxicology and Pharmaceutical Science
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5%
Other
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Unknown
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Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 8. 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 24 July 2019.
All research outputs
#6,310,403
of 33,052,206 outputs
Outputs from Cell Reports
#9,420
of 16,486 outputs
Outputs of similar age
#89,853
of 367,403 outputs
Outputs of similar age from Cell Reports
#221
of 315 outputs
Altmetric has tracked 33,052,206 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 16,486 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 26.9. This one is in the 42nd percentile – i.e., 42% of its peers scored the same or lower than it.
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