Publication

d-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity

Kirkwood, N. K., Derudas, M., Kenyon, E. J., Huckvale, R., van Netten, S., Ward, S., Richardson, G. P. & Kros, C. J., 5-Sep-2017, In : Frontiers in cellular neuroscience. 11, 15 p., 262.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Kirkwood, N. K., Derudas, M., Kenyon, E. J., Huckvale, R., van Netten, S., Ward, S., ... Kros, C. J. (2017). d-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity. Frontiers in cellular neuroscience, 11, [262]. https://doi.org/10.3389/fncel.2017.00262

Author

Kirkwood, Nerissa K. ; Derudas, Marco ; Kenyon, Emma J ; Huckvale, Rosemary ; van Netten, Sietse ; Ward, Simon ; Richardson, Guy P ; Kros, Corne J. / d-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity. In: Frontiers in cellular neuroscience. 2017 ; Vol. 11.

Harvard

Kirkwood, NK, Derudas, M, Kenyon, EJ, Huckvale, R, van Netten, S, Ward, S, Richardson, GP & Kros, CJ 2017, 'd-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity', Frontiers in cellular neuroscience, vol. 11, 262. https://doi.org/10.3389/fncel.2017.00262

Standard

d-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity. / Kirkwood, Nerissa K.; Derudas, Marco; Kenyon, Emma J ; Huckvale, Rosemary; van Netten, Sietse; Ward, Simon; Richardson, Guy P; Kros, Corne J.

In: Frontiers in cellular neuroscience, Vol. 11, 262, 05.09.2017.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Kirkwood NK, Derudas M, Kenyon EJ, Huckvale R, van Netten S, Ward S et al. d-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity. Frontiers in cellular neuroscience. 2017 Sep 5;11. 262. https://doi.org/10.3389/fncel.2017.00262


BibTeX

@article{a7981c6bf64b4b05a064bc8d7c7e8c85,
title = "d-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity",
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 Ca2+ 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.",
keywords = "ZEBRAFISH LATERAL-LINE, MAMMALIAN INNER-EAR, IN-VITRO, MECHANOTRANSDUCER CHANNEL, POTASSIUM CURRENT, DEATH PATHWAYS, MOUSE COCHLEA, CANCER CELLS, DANIO-RERIO, TMC1",
author = "Kirkwood, {Nerissa K.} and Marco Derudas and Kenyon, {Emma J} and Rosemary Huckvale and {van Netten}, Sietse and Simon Ward and Richardson, {Guy P} and Kros, {Corne J}",
year = "2017",
month = "9",
day = "5",
doi = "10.3389/fncel.2017.00262",
language = "English",
volume = "11",
journal = "Frontiers in cellular neuroscience",
issn = "1662-5102",
publisher = "Frontiers Media SA",

}

RIS

TY - JOUR

T1 - d-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity

AU - Kirkwood, Nerissa K.

AU - Derudas, Marco

AU - Kenyon, Emma J

AU - Huckvale, Rosemary

AU - van Netten, Sietse

AU - Ward, Simon

AU - Richardson, Guy P

AU - Kros, Corne J

PY - 2017/9/5

Y1 - 2017/9/5

N2 - 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 Ca2+ 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.

AB - 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 Ca2+ 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.

KW - ZEBRAFISH LATERAL-LINE

KW - MAMMALIAN INNER-EAR

KW - IN-VITRO

KW - MECHANOTRANSDUCER CHANNEL

KW - POTASSIUM CURRENT

KW - DEATH PATHWAYS

KW - MOUSE COCHLEA

KW - CANCER CELLS

KW - DANIO-RERIO

KW - TMC1

U2 - 10.3389/fncel.2017.00262

DO - 10.3389/fncel.2017.00262

M3 - Article

C2 - 28928635

VL - 11

JO - Frontiers in cellular neuroscience

JF - Frontiers in cellular neuroscience

SN - 1662-5102

M1 - 262

ER -

ID: 47424453