The effects of over-expression of the FK506-binding protein FKBP12.6 on K+ currents in adult rabbit ventricular myocytes

Kettlewell, S., Seidler, T. and Smith, G.L. (2009) The effects of over-expression of the FK506-binding protein FKBP12.6 on K+ currents in adult rabbit ventricular myocytes. Pflügers Archiv - European Journal of Physiology, 458(4), pp. 653-660. (doi:10.1007/s00424-009-0666-y)

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Publisher's URL: http://dx.doi.org/10.1007/s00424-009-0666-y

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 (Ito) 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 (IK1) by ~25% in the voltage range -70 to -30 mV, an effect prevented by FK506 or lowering intracellular [Ca2+] below 1 nM. Over-expression of an FKBP12.6 mutant, which cannot bind calcineurin, prolonged APD and affected Ito and IK1 in a similar manner to wild-type protein. These data suggest that FKBP12.6 can modulate APD via changes in IK1 independently of calcineurin binding, suggesting that FKBP12.6 may affect APD by direct interaction with IK1.

Item Type:Articles
Keywords:FKBP12.6; FKBP12.6 mutant; I(to); I(K1); action potential
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Godfrey and Kettlewell, Dr Sarah
Authors: Kettlewell, S., Seidler, T., and Smith, G.L.
Subjects:Q Science > QP Physiology
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Pflügers Archiv - European Journal of Physiology
ISSN:0031-6768
ISSN (Online):1432-2013
Published Online:31 March 2009

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