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<sup>+</sup> 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>I</i><sub>to</sub>) 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>I</i><sub>K1</sub>) by ~25% in the voltage range -70 to -30 mV, an effect prevented by FK506 or lowering intracellular [Ca<sup>2+</sup>] below 1 nM. Over-expression of an FKBP12.6 mutant, which cannot bind calcineurin, prolonged APD and affected <i>I</i><sub>to</sub> and <i>I</i><sub>K1</sub> in a similar manner to wild-type protein. These data suggest that FKBP12.6 can modulate APD via changes in <i>I</i><sub>K1</sub> independently of calcineurin binding, suggesting that FKBP12.6 may affect APD by direct interaction with <i>I</i><sub>K1</sub>.
| 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 > School of Cardiovascular & Metabolic Health |
| Journal Name: | Pflügers Archiv - European Journal of Physiology |
| ISSN: | 0031-6768 |
| ISSN (Online): | 1432-2013 |
| Published Online: | 31 March 2009 |
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