Author:
Kullmann F. Aura,Shah M. A.,Birder L. A.,de Groat W. C.
Abstract
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 4α-phorbol-12,13 didecanoate (4α-PDD; 1–5 μM) and the TRPA1/TRPM8 agonist icilin (50–100 μM) elicited transient currents in a high percentage of cells (>70%). 4α-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 4α-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.
Publisher
American Physiological Society
Cited by
83 articles.
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