Crotamine toxicity revisited: novel insights based on KV channel inhibition
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2012
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Biophysical Journal
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Crotamine, a 5KDa peptide possesses a unique biological versatility. Not only
its cell-penetrating activity has become of clinical interest but moreover, its potential
selective anti-tumor activity is of great pharmacological importance. Before,
several studies have attempted to elucidate the exact molecular target
responsible for the crotamine-induced skeletal muscle spasm. The aim of this
study was to investigate whether crotamine affects voltage-gated potassium
(KV) channels in an effort to explain its in vivo effects.
Crotamine was studied on ion channel function using the two-electrode voltage
clamp technique on 16 cloned ion channels (12 KV channels and 4 NaV channels),
expressed in Xenopus laevis oocytes.
Crotamine selectively inhibits KV1.1, KV1.2 and KV1.3 channels with an IC50
of ~300 nM and the key amino acids responsible for this molecular interaction
are highlighted. Our results demonstrate for the first time that the symptoms
which are observed in the typical crotamine syndrome may result from the inhibition
of KV channels.
The ability of crotamine to inhibit the potassium current through KV channels
unravels it as the first snake peptide with the unique multifunctionality such as
cell penetrating, antitumoral activity and KV channel inhibiting properties. The
potent and selective KV channel inhibiting properties, as demonstrated in this
work, can be an advantage for the use of crotamine or its derivatives as antitumor
drug. This new property of crotamine might explain some experimental
observations and opens new perspectives of pharmacological uses.
Como referenciar
TYTGAT, JAN; PEIGNEUR, STEVE; BELATO Y ORTS, DIEGO J.; SILVA, ALVARO P. da; OGUIURA, NANCY; BONI-MITAKE, MALVINA; ZAHARENKO, ANDRE J. Crotamine toxicity revisited: novel insights based on KV channel inhibition. Biophysical Journal, v. 102, n. 3, p. 658A - 658A, 2012. supl. 1. Disponível em: http://repositorio.ipen.br/handle/123456789/27618. Acesso em: 24 Apr 2024.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.