Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/110056
Title: ATP enhances spontaneous calcium activity in cultured suburothelial myofibroblasts of the human bladder
Authors: Cheng, Sheng
Scigalla, Frank Peter
di Fenizio, Pietro Speroni 
Zhang, Zhi Geng
Stolzenburg, Jens-Uwe
Neuhaus, Jochen
Issue Date: 2011
Publisher: Public Library of Science
Project: Deutsche Forschungsgemeinschaft (DFG) (JN:NE425/4-4 
Sir Run Run Shaw Hospital 
College of Medicine, Zhejiang University, Hangzhou, China 
Serial title, monograph or event: PLoS ONE
Volume: 6
Issue: 10
Abstract: Background: Suburothelial myofibroblasts (sMF) are located underneath the urothelium in close proximity to afferent nerves. They express purinergic receptors and show calcium transients in response to ATP. Therefore they are supposed to be involved in afferent signaling of the bladder fullness. Since ATP concentration is likely to be very low during the initial filling phase, we hypothesized that sMF Ca2+ activity is affected even at very low ATP concentrations. We investigated ATP induced modulation of spontaneous activity, intracellular calcium response and purinergic signaling in cultured sMF. Methodology/Principal Findings: Myofibroblast cultures, established from cystectomies, were challenged by exogenous ATP in presence or absence of purinergic antagonist. Fura-2 calcium imaging was used to monitor ATP (10216 to 1024 mol/l) induced alterations of calcium activity. Purinergic receptors (P2X1, P2X2, P2X3) were analysed by confocal immunofluorescence. We found spontaneous calcium activity in 55.18%61.65 of the sMF (N = 48 experiments). ATP significantly increased calcium activity even at 10216 mol/l. The calcium transients were partially attenuated by subtype selective antagonist (TNP-ATP, 1 mM; A-317491, 1 mM), and were mimicked by the P2X1, P2X3 selective agonist a,bmethylene ATP. The expression of purinergic receptor subtypes in sMF was confirmed by immunofluorescence. Conclusions/Significance: Our experiments demonstrate for the first time that ATP can modulate spontaneous activity and induce intracellular Ca2+ response in cultured sMF at very low concentrations, most likely involving P2X receptors. These findings support the notion that sMF are able to register bladder fullness very sensitively, which predestines them for the modulation of the afferent bladder signaling in normal and pathological conditions.
URI: https://hdl.handle.net/10316/110056
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0025769
Rights: openAccess
Appears in Collections:I&D CISUC - Artigos em Revistas Internacionais
FCTUC Eng.Informática - Artigos em Revistas Internacionais

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