Preferential closed channel blockade of HERG potassium currents by chemically synthesised BeKm-1 scorpion toxin.
FEBS Lett
; 547(1-3): 20-6, 2003 Jul 17.
Article
en En
| MEDLINE
| ID: mdl-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.
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Colección:
01-internacional
Asunto principal:
Venenos de Escorpión
/
Canales de Potasio
/
Transactivadores
/
Canales de Potasio con Entrada de Voltaje
/
Proteínas de Transporte de Catión
/
Bloqueadores de los Canales de Potasio
/
Proteínas de Unión al ADN
Límite:
Humans
Idioma:
En
Revista:
FEBS Lett
Año:
2003
Tipo del documento:
Article
País de afiliación:
Reino Unido