ArticleProceedings of the National Academy of Sciences of the United States of America1998
Inositol 1,4,5-trisphosphate [correction of tris-phosphate] activation of inositol trisphosphate [correction of tris-phosphate] receptor Ca2+ channel by ligand tuning of Ca2+ inhibition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 139 papers.
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Who cites it
139 citing papers in PubMed, 272 citations in OpenAlex.
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- Ligand sensitivity of type-1 inositol 1,4,5-trisphosphate receptor is enhanced by the D2594K mutation.Pflugers Archiv : European journal of physiology · 2023Article
- An integrate-and-fire approach to CaBiophysical journal · 2023Article
- Endocannabinoid signaling in astrocytes.Glia · 2023Review
- Conformational motions and ligand-binding underlying gating and regulation in IPNature communications · 2022Article
- Functional determination of calcium-binding sites required for the activation of inositol 1,4,5-trisphosphate receptors.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mechanisms and physiological implications of cooperative gating of clustered ion channels.Physiological reviews · 2022Review
- The discovery and development of IP3 receptor modulators: an update.Expert opinion on drug discovery · 2021Article
- The Calcium Signaling Mechanisms in Arterial Smooth Muscle and Endothelial Cells.Comprehensive Physiology · 2021Article
- Ion Channels in Glioma Malignancy.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Calcium-Handling Defects and Neurodegenerative Disease.Cold Spring Harbor perspectives in biology · 2020Review
79 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inositol 1,4,5-trisphosphate (IP3) [corrected] binding to its receptors (IP3R) in the endoplasmic reticulum (ER) activates Ca2+ release from the ER lumen to the cytoplasm, generating complex cytoplasmic Ca2+ concentration signals including temporal oscillations and propagating waves. IP3-mediated Ca2+ release is also controlled by cytoplasmic Ca2+ concentration with both positive and negative feedback. Single-channel properties of the IP3R in its native ER membrane were investigated by patch clamp electrophysiology of isolated Xenopus oocyte nuclei to determine the dependencies of IP3R on cytoplasmic Ca2+ and IP3 concentrations under rigorously defined conditions. Instead of the expected narrow bell-shaped cytoplasmic free Ca2+ concentration ([Ca2+]i) response centered at approximately 300 nM-1 microM, the open probability remained elevated (approximately 0.8) in the presence of saturating levels (10 microM) of IP3, even as [Ca2+]i was raised to high concentrations, displaying two distinct types of functional Ca2+ binding sites: activating sites with half-maximal activating [Ca2+]i (Kact) of 210 nM and Hill coefficient (Hact) approximately 2; and inhibitory sites with half-maximal inhibitory [Ca2+]i (Kinh) of 54 microM and Hill coefficient (Hinh) approximately 4. Lowering IP3 concentration was without effect on Ca2+ activation parameters or Hinh, but decreased Kinh with a functional half-maximal activating IP3 concentration (KIP3) of 50 nM and Hill coefficient (HIP3) of 4 for IP3. These results demonstrate that Ca2+ is a true receptor agonist, whereas the sole function of IP3 is to relieve Ca2+ inhibition of IP3R. Allosteric tuning of Ca2+ inhibition by IP3 enables the individual IP3R Ca2+ channel to respond in a graded fashion, which has implications for localized and global cytoplasmic Ca2+ concentration signaling and quantal Ca2+ release.
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