ArticleProceedings of the National Academy of Sciences of the United States of America2014
Decreased polycystin 2 expression alters calcium-contraction coupling and changes β-adrenergic signaling pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Investigating PKD2 deficiency-associated cardiomyopathies using hESC-cardiomyocytes and bioengineered 3D ventricular cardiac tissue strips.Cell death & disease · 2026Article
- Cardiovascular Complications in ADPKD.Kidney international reports · 2025Review
- The endoplasmic reticulum luminal CaPNAS nexus · 2025Article
- Review
- Aortic Dilatation in Children and Young People With ADPKD.Kidney international reports · 2024Article
- Cardiovascular perspectives of the TRP channel polycystin 2.The Journal of physiology · 2024Article
- Cardiovascular Manifestations and Management in ADPKD.Kidney international reports · 2023Review
- New N-aryl-N-alkyl-thiophene-2-carboxamide compound enhances intracellular CaBiophysical journal · 2023Article
- Arrhythmogenesis in the aged heart following ischaemia-reperfusion: role of transient receptor potential vanilloid 4.Cardiovascular research · 2022Article
- Role of PKD2 in the endoplasmic reticulum calcium homeostasis.Frontiers in physiology · 2022Review
- Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice.Scientific reports · 2021Article
- Article
- Deletion of cardiac polycystin 2/PC2 results in increased SR calcium release and blunted adrenergic reserve.American journal of physiology. Heart and circulatory physiology · 2020Article
- Transient receptor potential vanilloid-4 contributes to stretch-induced hypercontractility and time-dependent dysfunction in the aged heart.Cardiovascular research · 2020Article
- Polycystins, ADPKD, and Cardiovascular Disease.Kidney international reports · 2020Review
- Polycystin 2: A calcium channel, channel partner, and regulator of calcium homeostasis in ADPKD.Cellular signalling · 2020Review
- Cardiomyocyte d-dopachrome tautomerase protects against heart failure.JCI insight · 2019Article
- Transient receptor potential channels in cardiac health and disease.Nature reviews. Cardiology · 2019Review
- Novel approach for quantification of endoplasmic reticulum CaAmerican journal of physiology. Heart and circulatory physiology · 2019Article
- Polycystin 2 regulates mitochondrial CaScience signaling · 2019Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Cardiac disorders are the main cause of mortality in autosomal-dominant polycystic kidney disease (ADPKD). However, how mutated polycystins predispose patients with ADPKD to cardiac pathologies before development of renal dysfunction is unknown. We investigate the effect of decreased levels of polycystin 2 (PC2), a calcium channel that interacts with the ryanodine receptor, on myocardial function. We hypothesize that heterozygous PC2 mice (Pkd2(+/-)) undergo cardiac remodeling as a result of changes in calcium handling, separate from renal complications. We found that Pkd2(+/-) cardiomyocytes have altered calcium handling, independent of desensitized calcium-contraction coupling. Paradoxically, in Pkd2(+/-) mice, protein kinase A (PKA) phosphorylation of phospholamban (PLB) was decreased, whereas PKA phosphorylation of troponin I was increased, explaining the decoupling between calcium signaling and contractility. In silico modeling supported this relationship. Echocardiography measurements showed that Pkd2(+/-) mice have increased left ventricular ejection fraction after stimulation with isoproterenol (ISO), a β-adrenergic receptor (βAR) agonist. Blockers of βAR-1 and βAR-2 inhibited the ISO response in Pkd2(+/-) mice, suggesting that the dephosphorylated state of PLB is primarily by βAR-2 signaling. Importantly, the Pkd2(+/-) mice were normotensive and had no evidence of renal cysts. Our results showed that decreased PC2 levels shifted the βAR pathway balance and changed expression of calcium handling proteins, which resulted in altered cardiac contractility. We propose that PC2 levels in the heart may directly contribute to cardiac remodeling in patients with ADPKD in the absence of renal dysfunction.
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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.