Functional TRP and ASIC-like channels in cultured urothelial cells from the rat
Functional TRP and ASIC-like channels in cultured urothelial cells from the rat
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DOI：
10.1152/ajprenal.90718.2008
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发表时间：
2009-04-01
影响因子：
4.2
通讯作者：
de Groat, W. C.
中科院分区：
文献类型：
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作者：
Kullmann, F. Aura;Shah, M. A.;de Groat, W. C.
Kullmann FA，Shah MA，Birder LA，de Groat WC。培养的大鼠尿路上皮细胞中的功能性Trp和ASIC样通道。Am J Physiol Renal Physiol 296：F892-F901,2009。2009年1月21日首次出版；DOI：10.1152/ajprenal.90718.2008。-瞬时受体电位(Trp)和酸敏离子通道(ASIC)是感觉神经元中化学、机械、热和伤害刺激的分子检测器。它们已经在尿路上皮中被发现，尿路上皮被认为是膀胱感觉通路的一部分，在那里它们可能在膀胱功能中发挥作用。本研究利用膜片钳和Fura 2钙离子成像技术研究了培养的大鼠尿上皮细胞Trp和ASIC通道的功能特性。TRPV4激动剂4α-佛波醇-12，13-十二烷酸(4α-PDD；1-5µM)和TRPA1/TRPM8激动剂iclin(50-100µM)在高比例细胞(70%)上诱发瞬时电流。4TRPV4拮抗剂HC-010961(10 MU M)可抑制α-PDD反应。TRPV1激动剂辣椒素(1-100 mU M)和TRPA1/TRPM8激动剂薄荷醇(5-200 mU M)在中等比例(接近25%)的细胞上诱发瞬时电流。所有这些激动剂都增加了细胞内钙离子浓度([Ca~(2+)](I))。大多数细胞对一种以上的色氨酸激动剂(如辣椒素和4α-PDD)有反应，表明不同的色氨酸通道共表达。在TRPV1拮抗剂卡萨西平(10 MU M)存在下，HCl引起的pH变化引起离子电流(pH 5.5)和[Ca~(2+)](I)升高(pH 6.5)，接近50%的细胞。用冰醋酸(pH 5.5)改变pH可产生类双相电流。酸诱导的反应对阿米洛利(10mU M)敏感。综上所述，尿路上皮细胞表达多种Trp和ASIC通道，其激活引起离子电流和钙内流。这些“类神经元”特性可能与递质释放有关，如三磷酸腺苷，它可以作用于传入神经或平滑肌，调节它们对不同刺激的反应。
Kullmann FA, Shah MA, Birder LA, de Groat WC. Functional TRP and ASIC-like channels in cultured urothelial cells from the rat. Am J Physiol Renal Physiol 296: F892-F901, 2009. First published January 21, 2009; 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 Ca2+ imaging techniques. The TRPV4 agonist 4 alpha-phorbol-12,13 didecanoate (4 alpha-PDD; 1-5 mu M) and the TRPA1/TRPM8 agonist icilin (50-100 mu M) elicited transient currents in a high percentage of cells (>70%). 4 alpha-PDD responses were suppressed by the TRPV4 antagonist HC-010961 (10 mu M). The TRPV1 agonist capsaicin (1-100 mu M) and the TRPA1/TRPM8 agonist menthol (5-200 mu M) elicited transient currents in a moderate percentage of cells (similar to 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 alpha-PDD), indicating coexpression of different TRP channels. In the presence of the TRPV1 antagonist capsazepine (10 mu M), changes in pH induced by HCl elicited ionic currents (pH 5.5) and increased [Ca2+](i) (pH 6.5) in similar to 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 mu M). 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.