The Cardiac IKs Potassium Channel Macromolecular Complex Includes the Phosphodiesterase PDE4D3

Terrenoire, C., Houslay, M. D., Baillie, G. S. and Kass, R. S. (2009) The Cardiac IKs Potassium Channel Macromolecular Complex Includes the Phosphodiesterase PDE4D3. Journal of Biological Chemistry, 284(14), pp. 9140-9146. (doi:10.1074/jbc.M805366200)

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Publisher's URL: http://dx.doi.org/10.1074/jbc.M805366200

Abstract

The cardiac IKs potassium channel is a macromolecular complex consisting of a-(KCNQ1) and {beta}-subunits (KCNE1) and the A kinase anchoring protein (AKAP) Yotiao (AKAP-9) which recruits protein kinase (PKA) and protein phosphatase (PP1) to the channel. Here we have tested the hypothesis that specific cAMP phosphodiesterase (PDE) isoforms of the PDE4D family that are expressed in the heart are also part of the IKs signaling complex and contribute to its regulation by cAMP. PDE4D isoforms co-immunoprecipitated with IKs channels in hearts of mice expressing the IKs channel. In myocytes isolated from these mice IKs was increased by pharmacological PDE inhibition. PDE4D3, but not PDE4D5, co-immunoprecipitated with the IKs channel only in CHO cells co-expressing AKAP-9, and PDE4D3, but not PDE4D5, co-immunoprecipitated with AKAP-9. Functional experiments in CHO cells expressing AKAP-9 and either PDE4D3 or PDE4D5 isoforms revealed modulation of the IKs response to cAMP by PDE4D3 but not PDE4D5. We conclude that PDE4D3, like PKA and PP1, is recruited to the IKs channel via AKAP-9 and contributes to its critical regulation by cAMP

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Baillie, Professor George and Houslay, Professor Miles
Authors: Terrenoire, C., Houslay, M. D., Baillie, G. S., and Kass, R. S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Journal of Biological Chemistry
Journal Abbr.:J Biol Chem.
Publisher:American Society for Biochemistry and Molecular Biology, Inc.
ISSN:0021-9258
ISSN (Online):1083-351X
Published Online:13 February 2009
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
438301Phosphodiesterase-4 isoforms - intracellular targeting, regulation and potential therapeutic targetsMiles HouslayMedical Research Council (MRC)G0600765Institute of Neuroscience and Psychology
421571thera-cAMP: identification of therapeutic molecules to target compartmentalised cAMP signalling networks in human diseaseMiles HouslayEuropean Commission (EC)UNSPECIFIEDInstitute of Neuroscience and Psychology
432501Transatlantic networks of excellence in cardiovascular diseaseMiles HouslayFoundation Leducq (LEDUCQ-VIL)06 CVD 02Institute of Neuroscience and Psychology