The effects of over-expression of the FK506-binding protein FKBP12.6 on K+ currents in adult rabbit ventricular myocytes
Open Access
- 31 March 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Pflügers Archiv - European Journal of Physiology
- Vol. 458 (4), 653-660
- https://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 (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 [Ca2+] 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.Keywords
This publication has 64 references indexed in Scilit:
- Neutralizing Tumor-Promoting Chronic Inflammation: A Magic Bullet?Science, 2013
- Mechanisms of resistance to chemotherapeutic and anti-angiogenic drugs as novel targets for pancreatic cancer therapyFrontiers in Pharmacology, 2013
- Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretionNature, 2012
- Enzymatic Targeting of the Stroma Ablates Physical Barriers to Treatment of Pancreatic Ductal AdenocarcinomaCancer Cell, 2012
- Modulation of Pancreatic Cancer Chemoresistance by Inhibition of TAK1JNCI Journal of the National Cancer Institute, 2011
- FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic CancerNew England Journal of Medicine, 2011
- CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and HumansScience, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic CancerScience, 2009
- Modes of resistance to anti-angiogenic therapyNature Reviews Cancer, 2008