FKBP12.6 over-expression prolongs action potential duration in rabbit ventricular myocytes by directly interacting with the inward rectifier current (I(K1)), independent of calcineurin binding.
Caution against clinical translation from rabbit myocytes; leaves open FKBP12.6 role in human ventricular electrophysiology.
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).
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Kettlewell et al. (2009) studied this question.
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