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The role of ATP signalling in response to mechanical stimulation studied in T24 cells using new microphysiological tools
Department of Molecular Medicine and Surgery, Section of Urology, Karolinska Institutet, Stockholm, Sweden / Department of Urology, Karolinska University Hospital, Stockholm, Sweden / Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Section of Urology, Karolinska Institutet, Stockholm, Sweden / Department of Urology, Karolinska University Hospital, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Section of Urology, Karolinska Institutet, Stockholm, Sweden / Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Linköping University, Department of Physics, Chemistry and Biology, Sensor and Actuator Systems. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0002-2071-7768
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2018 (English)In: Journal of Cellular and Molecular Medicine (Print), ISSN 1582-1838, E-ISSN 1582-4934, Vol. 22, no 4, p. 2319-2328Article in journal (Refereed) Published
Abstract [en]

The capacity to store urine and initiate voiding is a valued characteristic of the human urinary bladder. To maintain this feature, it is necessary that the bladder can sense when it is full and when it is time to void. The bladder has a specialized epithelium called urothelium that is believed to be important for its sensory function. It has been suggested that autocrine ATP signalling contributes to this sensory function of the urothelium. There is well‐established evidence that ATP is released via vesicular exocytosis as well as by pannexin hemichannels upon mechanical stimulation. However, there are still many details that need elucidation and therefore there is a need for the development of new tools to further explore this fascinating field. In this work, we use new microphysiological systems to study mechanostimulation at a cellular level: a mechanostimulation microchip and a silicone‐based cell stretcher. Using these tools, we show that ATP is released upon cell stretching and that extracellular ATP contributes to a major part of Ca2+ signalling induced by stretching in T24 cells. These results contribute to the increasing body of evidence for ATP signalling as an important component for the sensory function of urothelial cells. This encourages the development of drugs targeting P2 receptors to relieve suffering from overactive bladder disorder and incontinence.

Place, publisher, year, edition, pages
Wiley , 2018. Vol. 22, no 4, p. 2319-2328
Keywords [en]
ATP, Ca2+ signalling, mechanostimulation, microphysiological systems, organ on chip, P2X, P2Y
National Category
Cell and Molecular Biology Cell Biology Neurosciences Immunology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:liu:diva-147345DOI: 10.1111/jcmm.13520ISI: 000428418200026OAI: oai:DiVA.org:liu-147345DiVA, id: diva2:1199019
Available from: 2018-04-19 Created: 2018-04-19 Last updated: 2018-05-17Bibliographically approved

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Jager, Edwin W. H.

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