The role of ATP signalling in response to mechanical stimulation studied in T24 cells using new microphysiological tools

• Published in: Journal of cellular and molecular medicine Vol. 22; no. 4; pp. 2319 - 2328
• Main Authors: Guan, Na N., Sharma, Nimish, Hallén‐Grufman, Katarina, Jager, Edwin W. H., Svennersten, Karl
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-04-2018; John Wiley and Sons Inc
• Subjects: Adenosine Triphosphate - genetics; Adenosine Triphosphate - metabolism; Animals; ATP; Autocrine Communication - genetics; Autocrine signalling; Bladder; Ca2+ signalling; Calcium ions; Calcium Signaling - genetics; Calcium signalling; Cell culture; Drug delivery; Drug development; Epithelium; Exocytosis; Exocytosis - genetics; Experiments; Humans; Mechanical stimuli; mechanostimulation; Mechanotransduction, Cellular - genetics; Medicin och hälsovetenskap; microphysiological systems; organ on chip; Original; P2X; P2Y; Phenols; Physiology; Polymers; Purine P2 receptors; Receptors, Purinergic P2 - genetics; Semiconductors; Silicones; Smooth muscle; Stimulation; Urinary bladder; Urinary Bladder - metabolism; Urinary Bladder - pathology; Urinary Incontinence - genetics; Urinary Incontinence - metabolism; Urinary Incontinence - pathology; Urine; Urothelium; Urothelium - metabolism; Urothelium - pathology; United States > US; microphysiological systems; organ on chip; mechanostimulation; P2Y; P2X; Ca2+ signalling; ATP
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.13520

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.