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

• Published in: American journal of physiology. Renal physiology Vol. 296; no. 4; p. F892
• Main Authors: Kullmann, F Aura, Shah, M A, Birder, L A, de Groat, W C
• Format: Journal Article
• Language: English
• Published: United States 01-04-2009
• Subjects: Acid Sensing Ion Channels; Animals; Ankyrins; Calcium Channels - metabolism; Calcium Signaling; Cells, Cultured; Female; Hydrogen-Ion Concentration; Male; Membrane Potentials; Membrane Transport Modulators - pharmacology; Microscopy, Fluorescence; Nerve Tissue Proteins - drug effects; Nerve Tissue Proteins - metabolism; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Sodium Channels - drug effects; Sodium Channels - metabolism; Time Factors; TRPA1 Cation Channel; TRPC Cation Channels - drug effects; TRPC Cation Channels - metabolism; TRPM Cation Channels - metabolism; TRPV Cation Channels - metabolism; Urinary Bladder - cytology; Urinary Bladder - drug effects; Urinary Bladder - metabolism; Urothelium - drug effects; Urothelium - metabolism
• ISSN: 1931-857X
• DOI: 10.1152/ajprenal.90718.2008

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 Ca(2+) imaging techniques. The TRPV4 agonist 4alpha-phorbol-12,13 didecanoate (4alpha-PDD; 1-5 microM) and the TRPA1/TRPM8 agonist icilin (50-100 microM) elicited transient currents in a high percentage of cells (>70%). 4alpha-PDD responses were suppressed by the TRPV4 antagonist HC-010961 (10 microM). The TRPV1 agonist capsaicin (1-100 microM) and the TRPA1/TRPM8 agonist menthol (5-200 microM) elicited transient currents in a moderate percentage of cells ( approximately 25%). All of these agonists increased intracellular calcium concentration ([Ca(2+)](i)). Most cells responded to more than one TRP agonist (e.g., capsaicin and 4alpha-PDD), indicating coexpression of different TRP channels. In the presence of the TRPV1 antagonist capsazepine (10 microM), changes in pH induced by HCl elicited ionic currents (pH 5.5) and increased [Ca(2+)](i) (pH 6.5) in approximately 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 microM). In summary, urothelial cells express multiple TRP and ASIC channels, whose activation elicits ionic currents and Ca(2+) 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.