DOI: 10.1016/s0014-5793(03)00662-8. Preferential closed channel blockade of HERG potassium currents by chemically synthesised BeKm‐1 scorpion toxin

Preferential closed channel blockade of HERG potassium currents by chemically synthesised BeKm‐1 scorpion toxin

10.1016/s0014-5793(03)00662-8

Crossref journal-article

Wiley

FEBS Letters (311)

Abstract

The scorpion toxin peptide BeKm‐1 was synthesised by fluorenylmethoxycarbonyl solid phase chemistry and folded by air oxidation. The peptide's effects on heterologous human ether‐a‐go‐go‐related gene potassium current (I HERG) in HEK293 cells were assessed using ‘whole‐cell’ patch clamp. Blockade of I HERG by BeKm‐1 was concentration‐dependent, temperature‐dependent, and rapid in onset and reversibility. Blockade also exhibited inverse voltage dependence, inverse dependence on duration of depolarisation, and reverse use‐ and frequency‐dependence. Blockade by BeKm‐1 and recombinant ergtoxin, another scorpion toxin known to block HERG, differed in their recovery from HERG current inactivation elicited by strong depolarisation and in their ability to block HERG when the channels were already activated. We conclude that synthetic BeKm‐1 toxin blocks HERG preferentially through a closed (resting) state channel blockade mechanism, although some open channel blockade also occurs.

Bibliography

Milnes, J. T., Dempsey, C. E., Ridley, J. M., Crociani, O., Arcangeli, A., Hancox, J. C., & Witchel, H. J. (2003). Preferential closed channel blockade of HERG potassium currents by chemically synthesised BeKmâ1 scorpion toxin. FEBS Letters, 547(1â3), 20â26. Portico.

Authors 7

James T Milnes (first)
Christopher E Dempsey (additional)
John M Ridley (additional)
Olivia Crociani (additional)
Annarosa Arcangeli (additional)
Jules C Hancox (additional)
Harry J Witchel (additional)

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Dates

Type	When
Created	22 years, 2 months ago (June 30, 2003, 9:57 a.m.)
Deposited	1 year, 11 months ago (Sept. 15, 2023, 11:59 p.m.)
Indexed	1 year ago (Aug. 12, 2024, 11:11 a.m.)
Issued	22 years, 2 months ago (June 19, 2003)
Published	22 years, 2 months ago (June 19, 2003)
Published Online	22 years, 2 months ago (June 19, 2003)
Published Print	22 years, 1 month ago (July 17, 2003)

Funders 0

None

BibTeX

@article{Milnes_2003, title={Preferential closed channel blockade of HERG potassium currents by chemically synthesised BeKm‐1 scorpion toxin}, volume={547}, ISSN={1873-3468}, url={http://dx.doi.org/10.1016/s0014-5793(03)00662-8}, DOI={10.1016/s0014-5793(03)00662-8}, number={1–3}, journal={FEBS Letters}, publisher={Wiley}, author={Milnes, James T and Dempsey, Christopher E and Ridley, John M and Crociani, Olivia and Arcangeli, Annarosa and Hancox, Jules C and Witchel, Harry J}, year={2003}, month=jun, pages={20–26} }

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