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Subunit and Frequency-Dependent Inhibition of Acid Sensing Ion Channels by Local Anesthetic Tetracaine

Overview of attention for article published in Molecular Pain, January 2013
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2 tweeters

Citations

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35 Dimensions

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32 Mendeley
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Title
Subunit and Frequency-Dependent Inhibition of Acid Sensing Ion Channels by Local Anesthetic Tetracaine
Published in
Molecular Pain, January 2013
DOI 10.1186/1744-8069-9-27
Pubmed ID
Authors

Tiandong Leng, Jun Lin, James E Cottrell, Zhi-Gang Xiong

Abstract

BACKGROUND: Extracellular acidosis is a prominent feature of multiple pathological conditions, correlating with pain sensation. Acid-sensing ion channels (ASICs), a family of proton-gated cation channels, are distributed throughout the central and peripheral nervous systems. Activation of ASICs, particularly ASIC3 and ASIC1a channels, by acidic pH and the resultant depolarization of nociceptive primary sensory neurons, participates in nociception. Agents that inhibit the activation of ASICs are thus expected to be analgesic. Here, we studied the effect of local anesthetic tetracaine on ASIC currents. RESULTS: Tetracaine inhibited the peak ASIC3 current in a concentration-dependent manner with an IC50 of 9.96 +/- 1.88 mM. The degree of inhibition by tetracaine was dependent on the extracellular pH but independent of the membrane potential. Furthermore, 3 mM tetracaine also inhibited 29.83% of the sustained ASIC3 current. In addition to ASIC3, tetracaine inhibited the ASIC1a and ASIC1beta currents. The inhibition of the ASIC1a current was influenced by the frequency of channel activation. In contrast to ASIC3, ASIC1a, and ASIC1beta currents, ASIC2a current was not inhibited by tetracaine. In cultured mouse dorsal root ganglion neurons, 1--3 mM tetracaine inhibited both the transient and sustained ASIC currents. At pH4.5, 3 mM tetracaine reduced the peak ASIC current to 60.06 +/- 4.51%, and the sustained current to 48.24 +/- 7.02% of the control values in dorsal root ganglion neurons. In contrast to ASICs, voltage-gated sodium channels were inhibited by acid, with 55.15% inhibition at pH6.0 and complete inhibition at pH5.0. CONCLUSIONS: These findings disclose a potential new mechanism underlying the analgesic effects of local anesthetics, particularly in acidic conditions where their primary target (i.e. voltage-gated Na+ channel) has been suppressed by protons.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Chile 1 3%
Unknown 31 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 25%
Researcher 7 22%
Student > Master 6 19%
Professor 2 6%
Other 2 6%
Other 3 9%
Unknown 4 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 7 22%
Medicine and Dentistry 7 22%
Biochemistry, Genetics and Molecular Biology 3 9%
Psychology 3 9%
Pharmacology, Toxicology and Pharmaceutical Science 2 6%
Other 4 13%
Unknown 6 19%

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 11 June 2013.
All research outputs
#7,244,682
of 12,552,259 outputs
Outputs from Molecular Pain
#195
of 464 outputs
Outputs of similar age
#69,167
of 148,808 outputs
Outputs of similar age from Molecular Pain
#13
of 22 outputs
Altmetric has tracked 12,552,259 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 464 research outputs from this source. They receive a mean Attention Score of 3.2. This one has gotten more attention than average, scoring higher than 55% of its peers.
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 148,808 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 22 others from the same source and published within six weeks on either side of this one. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.