The effects of over-expression of the FK506-binding protein FKBP12.6 on K(+) currents in adult rabbit ventricular myocytes.
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).
Kettlewell
S
S
Institute of Biomedical and Life Sciences, University of Glasgow, University Avenue, Glasgow, G12 8QQ, Scotland, UK.
Seidler
T
T
Smith
G L
GL