Referenced in: none

Automatically associated channels: Kv11.1

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

Authors: James T Milnes, Christopher E Dempsey, John M Ridley, Olivia Crociani, Annarosa Arcangeli, Jules C Hancox, Harry J Witchel

Journal, date & volume: FEBS Lett., 2003 Jul 17 , 547, 20-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12860380

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.