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X Demographics
Mendeley readers
Attention Score in Context
| Title |
d-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity
|
|---|---|
| Published in |
Frontiers in Cellular Neuroscience, September 2017
|
| DOI | 10.3389/fncel.2017.00262 |
| Pubmed ID | |
| Authors |
Nerissa K. Kirkwood, Molly O'Reilly, Marco Derudas, Emma J. Kenyon, Rosemary Huckvale, Sietse M. van Netten, Simon E. Ward, Guy P. Richardson, Corné J. Kros |
| Abstract |
Aminoglycoside antibiotics are widely used for the treatment of life-threatening bacterial infections, but cause permanent hearing loss in a substantial proportion of treated patients. The sensory hair cells of the inner ear are damaged following entry of these antibiotics via the mechano-electrical transducer (MET) channels located at the tips of the hair cell's stereocilia. d-Tubocurarine (dTC) is a MET channel blocker that reduces the loading of gentamicin-Texas Red (GTTR) into rat cochlear hair cells and protects them from gentamicin treatment. Berbamine is a structurally related alkaloid that reduces GTTR labeling of zebrafish lateral-line hair cells and protects them from aminoglycoside-induced cell death. Both compounds are thought to reduce aminoglycoside entry into hair cells through the MET channels. Here we show that dTC (≥6.25 μM) or berbamine (≥1.55 μM) protect zebrafish hair cells in vivo from neomycin (6.25 μM, 1 h). Protection of zebrafish hair cells against gentamicin (10 μM, 6 h) was provided by ≥25 μM dTC or ≥12.5 μM berbamine. Hair cells in mouse cochlear cultures are protected from longer-term exposure to gentamicin (5 μM, 48 h) by 20 μM berbamine or 25 μM dTC. Berbamine is, however, highly toxic to mouse cochlear hair cells at higher concentrations (≥30 μM) whilst dTC is not. The absence of toxicity in the zebrafish assays prompts caution in extrapolating results from zebrafish neuromasts to mammalian cochlear hair cells. MET current recordings from mouse outer hair cells (OHCs) show that both compounds are permeant open-channel blockers, rapidly and reversibly blocking the MET channel with half-blocking concentrations of 2.2 μM (dTC) and 2.8 μM (berbamine) in the presence of 1.3 mM Ca(2+) at -104 mV. Berbamine, but not dTC, also blocks the hair cell's basolateral K(+) current, IK,neo, and modeling studies indicate that berbamine permeates the MET channel more readily than dTC. These studies reveal key properties of MET-channel blockers required for the future design of successful otoprotectants. |
X Demographics
The data shown below were collected from the profiles of 8 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 25% |
| United Kingdom | 1 | 13% |
| Netherlands | 1 | 13% |
| Unknown | 4 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 7 | 88% |
| Scientists | 1 | 13% |
Mendeley readers
The data shown below were compiled from readership statistics for 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 50 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 8 | 16% |
| Student > Bachelor | 8 | 16% |
| Researcher | 7 | 14% |
| Student > Doctoral Student | 6 | 12% |
| Other | 3 | 6% |
| Other | 6 | 12% |
| Unknown | 12 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 9 | 18% |
| Agricultural and Biological Sciences | 5 | 10% |
| Neuroscience | 5 | 10% |
| Medicine and Dentistry | 5 | 10% |
| Engineering | 4 | 8% |
| Other | 8 | 16% |
| Unknown | 14 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. 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 21 September 2017.
All research outputs
#6,491,841
of 24,309,087 outputs
Outputs from Frontiers in Cellular Neuroscience
#1,168
of 4,515 outputs
Outputs of similar age
#96,611
of 319,394 outputs
Outputs of similar age from Frontiers in Cellular Neuroscience
#27
of 108 outputs
Altmetric has tracked 24,309,087 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 4,515 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.6. This one has gotten more attention than average, scoring higher than 74% 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 319,394 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 69% of its contemporaries.
We're also able to compare this research output to 108 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 75% of its contemporaries.