µ-conotoxin TsIIIA, a peptide inhibitor of human voltage-gated sodium channel hNav1.8.
Toxicon
; 186: 29-34, 2020 Oct 30.
Article
em En
| MEDLINE
| ID: mdl-32758497
ABSTRACT
TsIIIA, the first µ-conotoxin from Conus tessulatus, can selectively inhibit rat tetrodotoxin-resistant sodium channels. TsIIIA also shows potent analgesic activity in a mice hotplate analgesic assay, but its effect on human sodium channels remains unknown. In this study, eight human sodium channel subtypes, hNav1.1- hNav1.8, were expressed in HEK293 or ND7/23 cells and tested on the chemically synthesized TsIIIA. Patch clamp experiments showed that 10 µM TsIIIA had no effects on the tetrodotoxin-sensitive hNav1.1, hNav1.2, hNav1.3, hNav1.4, hNav1.6 and hNav1.7, as well as tetrodotoxin-resistant hNav1.5. For tetrodotoxin-resistant hNav1.8, concentrations of 1, 5 and 10 µM TsIIIA reduced the hNav1.8 currents to 59.26%, 36.21% and 24.93% respectively. Further detailed dose-effect experiments showed that TsIIIA inhibited hNav1.8 currents with an IC50 value of 2.11 µM. In addition, 2 µM TsIIIA did not induce a shift in the current-voltage relationship of hNav1.8. Taken together, the hNav1.8 peptide inhibitor TsIIIA provides a pharmacological probe for sodium channels and a potential therapeutic agent for pain.
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Base de dados:
MEDLINE
Assunto principal:
Conotoxinas
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Bloqueadores dos Canais de Sódio
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Caramujo Conus
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Canal de Sódio Disparado por Voltagem NAV1.7
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article