ArticleThe Journal of biological chemistry2009
The cardiac IKs potassium channel macromolecular complex includes the phosphodiesterase PDE4D3.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 144 citations in OpenAlex.
- Phosphodiesterase 8 regulation of excitation-contraction coupling as a target for cardiovascular disease: is it my turn now?American journal of physiology. Heart and circulatory physiology · 2026Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Review
- Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Article
- BI 1015550 is a PDE4B Inhibitor and a Clinical Drug Candidate for the Oral Treatment of Idiopathic Pulmonary Fibrosis.Frontiers in pharmacology · 2022Article
- Pharmacological rescue of specific long QT variants of KCNQ1/KCNE1 channels.Frontiers in physiology · 2022Article
- Calcineurin in the heart: New horizons for an old friend.Cellular signalling · 2021Review
- Epistatic interaction of PDE4DIP and DES mutations in familial atrial fibrillation with slow conduction.Human mutation · 2021Article
- Mechanisms of cAMP compartmentation in cardiac myocytes: experimental and computational approaches to understanding.The Journal of physiology · 2021Review
- Review
- Long QT syndrome - Bench to bedside.Heart rhythm O2 · 2021Article
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Calcineurin-AKAP interactions: therapeutic targeting of a pleiotropic enzyme with a little help from its friends.The Journal of physiology · 2020Review
- Cyclic AMP-Dependent Regulation of Kv7 Voltage-Gated Potassium Channels.Frontiers in physiology · 2020Review
- Nanometric targeting of type 9 adenylyl cyclase in heart.Biochemical Society transactions · 2019Review
- Regulation of ICells · 2019Article
- Rolipram, a PDE4 Inhibitor, Enhances the Inotropic Effect of Rat Heart by Activating SERCA2a.Frontiers in pharmacology · 2019Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The cardiac I(Ks) potassium channel is a macromolecular complex consisting of alpha-(KCNQ1) and beta-subunits (KCNE1) and the A kinase-anchoring protein (AKAP) Yotiao (AKAP-9), which recruits protein kinase A) and protein phosphatase 1 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 I(Ks) signaling complex and contribute to its regulation by cAMP. PDE4D isoforms co-immunoprecipitated with I(Ks) channels in hearts of mice expressing the I(Ks) channel. In myocytes isolated from these mice, I(Ks) was increased by pharmacological PDE inhibition. PDE4D3, but not PDE4D5, co-immunoprecipitated with the I(Ks) channel only in Chinese hamster ovary cells co-expressing AKAP-9, and PDE4D3, but not PDE4D5, co-immunoprecipitated with AKAP-9. Functional experiments in Chinese hamster ovary cells expressing AKAP-9 and either PDE4D3 or PDE4D5 isoforms revealed modulation of the I(Ks) response to cAMP by PDE4D3 but not PDE4D5. We conclude that PDE4D3, like protein kinase A and protein phosphatase 1, is recruited to the I(Ks) channel via AKAP-9 and contributes to its critical regulation by cAMP.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.