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A dietary fatty acid counteracts neuronal mechanical sensitization

Author

Listed:
  • Luis O. Romero

    (University of Tennessee Health Science Center
    College of Graduate Health Sciences)

  • Rebeca Caires

    (University of Tennessee Health Science Center)

  • Alec R. Nickolls

    (National Institutes of Health
    National Institutes of Health)

  • Alexander T. Chesler

    (National Institutes of Health
    National Institutes of Health)

  • Julio F. Cordero-Morales

    (University of Tennessee Health Science Center)

  • Valeria Vásquez

    (University of Tennessee Health Science Center)

Abstract

PIEZO2 is the essential transduction channel for touch discrimination, vibration, and proprioception. Mice and humans lacking Piezo2 experience severe mechanosensory and proprioceptive deficits and fail to develop tactile allodynia. Bradykinin, a proalgesic agent released during inflammation, potentiates PIEZO2 activity. Molecules that decrease PIEZO2 function could reduce heightened touch responses during inflammation. Here, we find that the dietary fatty acid margaric acid (MA) decreases PIEZO2 function in a dose-dependent manner. Chimera analyses demonstrate that the PIEZO2 beam is a key region tuning MA-mediated channel inhibition. MA reduces neuronal action potential firing elicited by mechanical stimuli in mice and rat neurons and counteracts PIEZO2 sensitization by bradykinin. Finally, we demonstrate that this saturated fatty acid decreases PIEZO2 currents in touch neurons derived from human induced pluripotent stem cells. Our findings report on a natural product that inhibits PIEZO2 function and counteracts neuronal mechanical sensitization and reveal a key region for channel inhibition.

Suggested Citation

  • Luis O. Romero & Rebeca Caires & Alec R. Nickolls & Alexander T. Chesler & Julio F. Cordero-Morales & Valeria Vásquez, 2020. "A dietary fatty acid counteracts neuronal mechanical sensitization," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16816-2
    DOI: 10.1038/s41467-020-16816-2
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    Cited by:

    1. Shilong Yang & Xinwen Miao & Steven Arnold & Boxuan Li & Alan T. Ly & Huan Wang & Matthew Wang & Xiangfu Guo & Medha M. Pathak & Wenting Zhao & Charles D. Cox & Zheng Shi, 2022. "Membrane curvature governs the distribution of Piezo1 in live cells," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Alia M. Obeidat & Matthew J. Wood & Natalie S. Adamczyk & Shingo Ishihara & Jun Li & Lai Wang & Dongjun Ren & David A. Bennett & Richard J. Miller & Anne-Marie Malfait & Rachel E. Miller, 2023. "Piezo2 expressing nociceptors mediate mechanical sensitization in experimental osteoarthritis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Luis O. Romero & Rebeca Caires & A. Kaitlyn Victor & Juanma Ramirez & Francisco J. Sierra-Valdez & Patrick Walsh & Vincent Truong & Jungsoo Lee & Ugo Mayor & Lawrence T. Reiter & Valeria Vásquez & Jul, 2023. "Linoleic acid improves PIEZO2 dysfunction in a mouse model of Angelman Syndrome," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Matthew Gabrielle & Yevgen Yudin & Yujue Wang & Xiaoyang Su & Tibor Rohacs, 2024. "Phosphatidic acid is an endogenous negative regulator of PIEZO2 channels and mechanical sensitivity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Clement Verkest & Irina Schaefer & Timo A. Nees & Na Wang & Juri M. Jegelka & Francisco J. Taberner & Stefan G. Lechner, 2022. "Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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