Functional architecture of inositol 1,4,5-trisphosphate signaling in restricted spaces of myoendothelial projections
| Autor: | Jonathan Ledoux, Yvonne Tallini, Adrian D. Bonev, Bo Shui, Michael I. Kotlikoff, Rachael M. Hannah, Mark S. Taylor, Viktoriya Solodushko, Mark T. Nelson |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Myocytes Smooth Muscle Inositol 1 4 5-Trisphosphate Biology Mice Potassium Channels Calcium-Activated chemistry.chemical_compound Internal medicine medicine Animals Inositol 1 4 5-Trisphosphate Receptors Myocyte Inositol Multidisciplinary Ryanodine receptor Endoplasmic reticulum Depolarization Biological Sciences Potassium channel Endocrinology chemistry Biophysics Calcium Cell Surface Extensions Endothelium Vascular Signal transduction Intracellular Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 105:9627-9632 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0801963105 |
| Popis: | Calcium (Ca 2+ ) release through inositol 1,4,5-trisphosphate receptors (IP 3 Rs) regulates the function of virtually every mammalian cell. Unlike ryanodine receptors, which generate local Ca 2+ events (“sparks”) that transmit signals to the juxtaposed cell membrane, a similar functional architecture has not been reported for IP 3 Rs. Here, we have identified spatially fixed, local Ca 2+ release events (“pulsars”) in vascular endothelial membrane domains that project through the internal elastic lamina to adjacent smooth muscle membranes. Ca 2+ pulsars are mediated by IP 3 Rs in the endothelial endoplasmic reticulum of these membrane projections. Elevation of IP 3 by the endothelium-dependent vasodilator, acetylcholine, increased the frequency of Ca 2+ pulsars, whereas blunting IP 3 production, blocking IP 3 Rs, or depleting endoplasmic reticulum Ca 2+ inhibited these events. The elementary properties of Ca 2+ pulsars were distinct from ryanodine-receptor-mediated Ca 2+ sparks in smooth muscle and from IP 3 -mediated Ca 2+ puffs in Xenopus oocytes. The intermediate conductance, Ca 2+ -sensitive potassium (K Ca 3.1) channel also colocalized to the endothelial projections, and blockage of this channel caused an 8-mV depolarization. Inhibition of Ca 2+ pulsars also depolarized to a similar extent, and blocking K Ca 3.1 channels was without effect in the absence of pulsars. Our results support a mechanism of IP 3 signaling in which Ca 2+ release is spatially restricted to transmit intercellular signals. |
| Databáze: | OpenAIRE |
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