Computational modeling of inhibitory signal transduction in urinary bladder PDGFRα+ cells

Amritanshu Gupta and Rohit Manchanda

Computer Methods in Biomechanics and Biomedical Engineering, 2024, vol. 27, issue 9, 1161-1170

Abstract: A crucial aspect of bladder function is the maintenance of a normo-active detrusor during bladder filling. The physiological mechanisms and pathways underlying this function are yet to be fully elucidated. Premature detrusor contractions are a key phenotype in detrusor overactivity, a common pathophysiological condition of the urinary bladder. Recent literature has identified PDFGRα+ cells as mediators in transducing inhibitory signals to detrusor smooth muscle cells via gap junctions. We employ computational modeling to study transduction pathways via which inhibitory signals are generated in PDFGRα+ cells in response to purinergic, nitrergic and mechanical stimuli. The key focus of our study here is to explore the effect of ATP, stretch and NO on the membrane potential of PDFGRα+ cells, which is driven to hyperpolarized potentials via the activation of SK3 channels. Our results indicate that purinergic, mechanical and nitrergic inputs can induce significant membrane hyperpolarizations of 20–35 mV relative to the resting membrane potential. Given the interconnections between PDFGRα+ cells and detrusor SMCs through gap junctions, these hyperpolarizations can have significant functional implications in the maintenance of a normo-active detrusor as also in departures from this state as seen in detrusor overactivity.

Date: 2024
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DOI: 10.1080/10255842.2023.2234063

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