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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/F892    most recent 90718.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kullmann, F. A. Articles by de Groat, W. C. Search for Related Content PubMed PubMed Citation Articles by Kullmann, F. A. Articles by de Groat, W. C.

Functional TRP and ASIC-like channels in cultured urothelial cells from the rat

Departments of ¹Pharmacology and Chemical Biology, ²Medicine, and ³Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Submitted 1 December 2008 ; accepted in final form 19 January 2009

Transient receptor potential (TRP) and acid-sensing ion channels (ASIC) are molecular detectors of chemical, mechanical, thermal, and nociceptive stimuli in sensory neurons. They have been identified in the urothelium, a tissue considered part of bladder sensory pathways, where they might play a role in bladder function. This study investigated functional properties of TRP and ASIC channels in cultured urothelial cells from the rat using patch-clamp and fura 2 Ca²⁺ imaging techniques. The TRPV4 agonist 4-phorbol-12,13 didecanoate (4-PDD; 1–5 µM) and the TRPA1/TRPM8 agonist icilin (50–100 µM) elicited transient currents in a high percentage of cells (>70%). 4-PDD responses were suppressed by the TRPV4 antagonist HC-010961 (10 µM). The TRPV1 agonist capsaicin (1–100 µM) and the TRPA1/TRPM8 agonist menthol (5–200 µM) elicited transient currents in a moderate percentage of cells (25%). All of these agonists increased intracellular calcium concentration ([Ca²⁺]_i). Most cells responded to more than one TRP agonist (e.g., capsaicin and 4-PDD), indicating coexpression of different TRP channels. In the presence of the TRPV1 antagonist capsazepine (10 µM), changes in pH induced by HCl elicited ionic currents (pH 5.5) and increased [Ca²⁺]_i (pH 6.5) in 50% of cells. Changes in pH using acetic acid (pH 5.5) elicited biphasic-like currents. Responses induced by acid were sensitive to amiloride (10 µM). In summary, urothelial cells express multiple TRP and ASIC channels, whose activation elicits ionic currents and Ca²⁺ influx. These "neuron-like" properties might be involved in transmitter release, such as ATP, that can act on afferent nerves or smooth muscle to modulate their responses to different stimuli.

bladder; fura 2 calcium imaging; patch clamp