Cited by 168Adenosine and Purinergic SignalingCalcium signaling and nucleotide metabolismIon Channels and Receptors

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Extracellular ATP induces oscillations of intracellular Ca 2+ and membrane potential and promotes transcription of IL-6 in macrophages

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Hanley, Peter J., Musset, Boris, Renigunta, Vijay, Limberg, Sven H., Dalpke, Alexander H., Sus, Rainer, Heeg, Klaus M., Preisig-Müller, Regina, Daut, Jürgen·2004·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0400733101PMC PMC439002

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Abstract

The effects of low concentrations of extracellular ATP on cytosolic Ca 2+ , membrane potential, and transcription of IL-6 were studied in monocyte-derived human macrophages. During inflammation or infection many cells secrete ATP. We show here that application of 10 μM ATP or 10 μM UTP induces oscillations in cytosolic Ca 2+ with a frequency of ≈12 min -1 and oscillations in membrane potential. RT-PCR analysis showed expression of P2Y 1 , P2Y 2 , P2Y 11 , P2X 1 , P2X 4 , and P2X 7 receptors, large-conductance ( KCNMA1 and KCNMB1–4 ), and intermediate-conductance ( KCNN4 ) Ca 2+ -activated K + channels. The Ca 2+ oscillations were unchanged after removal of extracellular Ca 2+ , indicating that they were mainly due to movements of Ca 2+ between intracellular compartments. Comparison of the effects of different nucleotides suggests that the Ca 2+ oscillations were elicited by activation of P2Y 2 receptors coupled to phospholipase C. Patch–clamp experiments showed that ATP induced a transient depolarization, probably mediated by activation of P2X 4 receptors, followed by membrane potential oscillations due to opening of Ca 2+ -activated K + channels. We also found that 10 μM ATPγS increased transcription of IL-6 ≈40-fold within 2 h. This effect was abolished by blockade of P2Y receptors with 100 μM suramin. Our results suggest that ATP released from inflamed, damaged, or metabolically impaired cells represents a “danger signal” that plays a major role in activating the innate immune system.

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Authors: Hanley, P. J., Musset, B., Renigunta, V., Limberg, S. H., Dalpke, A. H., Sus, R., Heeg, K. M., Preisig-Müller, R., & Daut, J.
Affiliations: Philipps University of Marburg (DE)
Institute of Physiology, Marburg University, Deutschhausstrasse 2, 35037 Marburg, Germany; and Institute of Microbiology, Marburg University, Pilgrimstein 2, 35037 Marburg, Germany
ORCID: Musset, Boris
Renigunta, Vijay
Dalpke, Alexander H.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2004-06-11
Volume: 101
Issue: 25
Pages: 9479-9484
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0400733101
PMC: PMC439002
OpenAlex: W2000714729
Cited by: 168
References: 37
Citations by year: 2026: 2 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 7 · 2016: 6 · 2015: 8 · 2014: 11 · 2013: 12 · 2012: 6
FWCI: 5.06
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords: extracellular ATP, calcium oscillations, membrane potential oscillations, macrophages, P2Y receptors, P2X4 receptor, P2X7 receptor, P2Y2 receptor, purinergic signaling, ATP gamma S, suramin, phospholipase C, calcium-activated potassium channels, damage-associated molecular patterns, innate immunity
MeSH terms: Adenosine Triphosphate, Calcium, Cells, Cultured, Gene Expression Regulation, Humans, Macrophages, Membrane Potentials, Molecular Sequence Data, Oscillometry, Sodium, Transcription, Genetic, Interleukin-6, Receptors, Purinergic P2, Patch-Clamp Techniques, Calcium Signaling, Large-Conductance Calcium-Activated Potassium Channel alpha Subunits

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Extracellular ATP induces oscillations of intracellular Ca 2+ and membrane potential and promotes transcription of IL-6 in macrophages

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