ArticleThe Journal of biological chemistry2010
Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) potentiates cardiac contractility via activation of the ryanodine receptor.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- PtdIns(3,5)PNature · 2026Article
- PtdIns(3,5)PbioRxiv : the preprint server for biology · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Recent advances of myotubularin-related (MTMR) protein family in cardiovascular diseases.Frontiers in cardiovascular medicine · 2024Review
- A plant virus hijacks phosphatidylinositol-3,5-bisphosphate to escape autophagic degradation in its insect vector.Autophagy · 2023Article
- Fibroblast growth factor 23 does not directly influence skeletal muscle cell proliferation and differentiation or ex vivo muscle contractility.American journal of physiology. Endocrinology and metabolism · 2018Article
- mTORC1 controls lysosomal CaScience signaling · 2018Article
- Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype.Nature communications · 2018Article
- Skeletal Muscle, but not Cardiovascular Function, Is Altered in a Mouse Model of Autosomal Recessive Hypophosphatemic Rickets.Frontiers in physiology · 2016Article
- Expression of Ca²⁺-permeable two-pore channels rescues NAADP signalling in TPC-deficient cells.The EMBO journal · 2015Article
- Cardiac thromboxane A2 receptor activation does not directly induce cardiomyocyte hypertrophy but does cause cell death that is prevented with gentamicin and 2-APB.BMC pharmacology & toxicology · 2014Article
- Phosphatidylinositol 3,5-bisphosphate: low abundance, high significance.BioEssays : news and reviews in molecular, cellular and developmental biology · 2014Review
- Lipid sorting and multivesicular endosome biogenesis.Cold Spring Harbor perspectives in biology · 2013Review
- Murine Fig4 is dispensable for muscle development but required for muscle function.Skeletal muscle · 2013Article
- Phosphoinositides: tiny lipids with giant impact on cell regulation.Physiological reviews · 2013Review
- FGF23 is a novel regulator of intracellular calcium and cardiac contractility in addition to cardiac hypertrophy.American journal of physiology. Endocrinology and metabolism · 2013Article
- Design, conduct, and analysis of a multicenter, pharmacogenomic, biomarker study in matched patients with severe sepsis treated with or without drotrecogin Alfa (activated).Annals of intensive care · 2012Article
- Phosphoinositides in the mammalian endo-lysosomal network.Sub-cellular biochemistry · 2012Review
- Store-operated calcium entry is present in HL-1 cardiomyocytes and contributes to resting calcium.Biochemical and biophysical research communications · 2011Article
- Fig4 deficiency: a newly emerged lysosomal storage disorder?Progress in neurobiologyReview
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) is the most recently identified phosphoinositide, and its functions have yet to be fully elucidated. Recently, members of our muscle group have shown that PI(3,5)P2 plays an important role in skeletal muscle function by altering Ca(2+) homeostasis. Therefore, we hypothesized that PI(3,5)P2 may also modulate cardiac muscle contractility by altering intracellular Ca(2+) ([Ca(2+)](i)) in cardiac myocytes. We first confirmed that PI(3,5)P2 was present and increased by insulin treatment of cardiomyocytes via immunohistochemistry. To examine the acute effects of PI(3,5)P2 treatment, electrically paced left ventricular muscle strips were incubated with PI(3,5)P2. Treatment with PI(3,5)P2 increased the magnitude of isometric force, the rate of force development, and the area associated with the contractile waveforms. These enhanced contractile responses were also observed in MIP/Mtmr14(-/-) mouse hearts, which we found to have elevated levels of PI(3,5)P2. In cardiac myocytes loaded with fura-2, PI(3,5)P2 produced a robust elevation in [Ca(2+)](i). The PI(3,5)P2-induced elevation of [Ca(2+)](i) was not present in conditions free of extracellular Ca(2+) and was completely blocked by ryanodine. We investigated whether the phosphoinositide acted directly with the Ca(2+) release channels of the sarcoplasmic reticulum (ryanodine receptors; RyR2). PI(3,5)P2 increased [(3)H]ryanodine binding and increased the open probability (P(o)) of single RyR2 channels reconstituted in lipid bilayers. This strongly suggests that the phosphoinositide binds directly to the RyR2 channel. Thus, we provide inaugural evidence that PI(3,5)P2 is a powerful activator of sarcoplasmic reticulum Ca(2+) release and thereby modulates cardiac contractility.
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