The effects of over-expression of the FK506-binding protein FKBP12.6 on K(+) currents in adult rabbit ventricular myocytes.
Pflugers Arch
; 458(4): 653-60, 2009 Aug.
Article
em En
| MEDLINE
| ID: mdl-19333617
ABSTRACT
This study examines the effects of the intracellular protein FKBP12.6 on action potential and associated K(+) currents in isolated adult rabbit ventricular cardiomyocytes. FKBP12.6 was over-expressed by ~6 times using a recombinant adenovirus coding for human FKBP12.6. This over-expression caused prolongation of action potential duration (APD) by ~30%. The amplitude of the transient outward current (I (to)) was unchanged, but rate of inactivation at potentials positive to +40 mV was increased. FKBP12.6 over-expression decreased the amplitude of the inward rectifier current (I (K1)) by ~25% in the voltage range -70 to -30 mV, an effect prevented by FK506 or lowering intracellular [Ca(2+)] below 1 nM. Over-expression of an FKBP12.6 mutant, which cannot bind calcineurin, prolonged APD and affected I (to) and I (K1) in a similar manner to wild-type protein. These data suggest that FKBP12.6 can modulate APD via changes in I (K1) independently of calcineurin binding, suggesting that FKBP12.6 may affect APD by direct interaction with I (K1).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Potássio
/
Potenciais de Ação
/
Função Ventricular Esquerda
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Proteínas de Ligação a Tacrolimo
/
Miócitos Cardíacos
/
Potenciais da Membrana
Limite:
Animals
Idioma:
En
Revista:
Pflugers Arch
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Reino Unido