The scorpion toxin peptide BeKm-1 was synthesised by £uorenylmethoxycarbonyl solid phase chemistry and folded by air oxidation. The peptide’s e¡ects on heterologous human ether-a-go-go-related gene potassium current (IHERG) in HEK293 cells were assessed using ‘whole-cell’ patch clamp. Blockade of IHERG 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.

Preferential closed channel blockade of HERG potassium currents by chemically synthesised BeKm-1 scorpion toxin / MILNES JT; DEMPSEY CE; RIDLEY JM; O. CROCIANI; ARCANGELI A; HANCOX JC; WITCHEL HJ. - In: FEBS LETTERS. - ISSN 0014-5793. - STAMPA. - 547:(2003), pp. 20-26.

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

CROCIANI, OLIVIA;ARCANGELI, ANNAROSA;
2003

Abstract

The scorpion toxin peptide BeKm-1 was synthesised by £uorenylmethoxycarbonyl solid phase chemistry and folded by air oxidation. The peptide’s e¡ects on heterologous human ether-a-go-go-related gene potassium current (IHERG) in HEK293 cells were assessed using ‘whole-cell’ patch clamp. Blockade of IHERG 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.
2003
547
20
26
MILNES JT; DEMPSEY CE; RIDLEY JM; O. CROCIANI; ARCANGELI A; HANCOX JC; WITCHEL HJ
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/251320
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