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The urinary bladder epithelium comprises a specialised population of superficially placed cells called the umbrella cells. The apical membrane domain of umbrella cells has several intriguing morphological properties and is the site for various signaling activities. A key function of umbrella cells is to sense mechanical stimuli as the bladder stretches in response to filling. More specifically, the mechanotransduction of stretch into subcellular signals is brought about by the activation of Piezo1 channels that mediate calcium into the cell interior. The incoming calcium is critical to several aspects of umbrella cell signaling, including regulation of exocytosis, ATP release and downstream purinergic signaling. We report here a computational framework that models stretch-induced mechanotransduction via Piezo1 channels and the resulting calcium signaling in umbrella cells factoring in morphological details of subcellular compartment volumes. Our results show the following: (i) activation of Piezo1 conductance in response to stretch; (ii) development of varying Piezo1 mediated [Ca 2+ ] profiles in subcellular compartments, namely, the apical sub-plasma membrane space, cytosol and mitochondria. The varying calcium amplitudes and temporal profiles in the subcellular compartments indicate highly specialised roles for stretch-mediated calcium in umbrella cells, including its potential effect on the energetics of mitochondria and the regulation of exocytosis.

Computational modeling of stretch induced calcium signaling at the apical membrane domain in umbrella cells