Sánchez-Freire, V; Blanchard, M G; Burkhard, F C; Kessler, T M; Kellenberger, S; Monastyrskaya, K (2011). Acid-sensing channels in human bladder: expression, function and alterations during bladder pain syndrome. The Journal of Urology, 186(4):1509-1516.
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PURPOSE: We examined the possible role of H(+) activated acid-sensing ion channels in pain perception. We characterized expression in bladder dome biopsies from patients with bladder pain syndrome and controls, in cultured human urothelium and in urothelial TEU-2 cells. MATERIALS AND METHODS: Cold cut biopsies from the bladder dome were obtained in 8 asymptomatic controls and 28 patients with bladder pain syndrome symptoms. Acid-sensing ion channel expression was analyzed by quantitative real-time polymerase chain reaction and immunofluorescence. Channel function was measured by electrophysiology. RESULTS: Acid-sensing ion channel 1a, 2a and 3 mRNA was detected in the human bladder. Similar amounts of acid-sensing ion channel 1a and 3 were detected in detrusor smooth muscle while in urothelium acid-sensing ion channel 3 levels were higher than levels of acid-sensing ion channel 1a. Acid-sensing ion channel 2a mRNA levels were lower than acid-sensing ion channel 1a and 3 levels in each layer. Acid-sensing ion channel currents were measured in TEU-2 cells and in primary cultures of human urothelium. Activated acid-sensing ion channel expression was confirmed by quantitative real-time polymerase chain reaction. TEU-2 cell differentiation caused acid-sensing ion channel 2a and 3 mRNA up-regulation, and acid-sensing ion channel 1a mRNA down-regulation. Patients with bladder pain syndrome showed up-regulation of acid-sensing ion channel 2a and 3 mRNA but acid-sensing ion channel 1a remained unchanged. In contrast, transient receptor potential vanilloid 1 mRNA was down-regulated during bladder pain syndrome. All differences were statistically significant (p <0.05). CONCLUSIONS: Several acid-sensing ion channel subunits are expressed in human bladder and TEU-2 cells, in which levels are regulated during urothelial differentiation. Up-regulation of acid-sensing ion channel 2a and 3 in patients with bladder pain syndrome suggests involvement in increased pain and hyperalgesia. Down-regulation of transient receptor potential vanilloid 1 mRNA might indicate that a different regulatory mechanism controls its expression in the human bladder. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Balgrist University Hospital, Swiss Spinal Cord Injury Center|
|Dewey Decimal Classification:||610 Medicine & health|
|Deposited On:||21 Feb 2012 19:36|
|Last Modified:||23 Jan 2015 11:31|
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