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

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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Milnes JT,Dempsey CE,Ridley JM,Crociani O,Arcangeli A,Hancox JC,Witchel HJ

doi

10.1016/s0014-5793(03)00662-8

keywords:

subject

Has Abstract

pub_date

2003-07-17 00:00:00

pages

20-6

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S0014579303006628

journal_volume

547

pub_type

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