Acquired long QT syndrome and phosphoinositide 3-kinase.
Trends Cardiovasc Med
; 27(7): 451-459, 2017 10.
Article
em En
| MEDLINE
| ID: mdl-28687226
ABSTRACT
While it is well known that mutation of several different ion channels can cause congenital long QT syndrome, block of IKr is widely thought to be responsible for most cases of drug-induced acquired long QT syndrome (aLQTS). In this article, we review evidence supporting another cause of aLQTS due to inhibition of phosphoinositide 3-kinase (PI3K) signaling. Inhibition of PI3K affects multiple plateau currents, reducing IKr, IKs, and ICaL while increasing the persistent sodium current (INaP). The effects of PI3K inhibitors develop slowly, requiring hours to days to reach steady state. Dofetilide and terfenadine, an antihistamine on which much of the original IKr hypothesis was based, are among the many drugs that inhibit the PI3K pathway. Reduced PI3K signaling may also play a role in aLQTS associated with diabetes. Drug safety testing to identify aLQTS risk may be improved by examining PI3K-dependent effects that develop over time.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome do QT Longo
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Inibidores de Proteínas Quinases
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Inibidores de Fosfoinositídeo-3 Quinase
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Sistema de Condução Cardíaco
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Frequência Cardíaca
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Trends Cardiovasc Med
Ano de publicação:
2017
Tipo de documento:
Article