Richter Trevor A, Dvoryanchikov Gennady A, Chaudhari Nirupa, Roper Stephen D
Dept. of Physiology and Biophysics, University of Miami School of Medicine, 1600 NW 10th Avenue, Miami, FL 33136, USA.
J Neurophysiol. 2004 Sep;92(3):1928-36. doi: 10.1152/jn.00273.2004. Epub 2004 May 12.
Sour (acid) taste is postulated to result from intracellular acidification that modulates one or more acid-sensitive ion channels in taste receptor cells. The identity of such channel(s) remains uncertain. Potassium channels, by regulating the excitability of taste cells, are candidates for acid transducers. Several 2-pore domain potassium leak conductance channels (K(2)P family) are sensitive to intracellular acidification. We examined their expression in mouse vallate and foliate taste buds using RT-PCR, and detected TWIK-1 and -2, TREK-1 and -2, and TASK-1. Of these, TWIK-1 and TASK-1 were preferentially expressed in taste cells relative to surrounding nonsensory epithelium. The related TRESK channel was not detected, whereas the acid-insensitive TASK-2 was. Using confocal imaging with pH-, Ca(2+)-, and voltage-sensitive dyes, we tested pharmacological agents that are diagnostic for these channels. Riluzole (500 microM), selective for TREK-1 and -2 channels, enhanced acid taste responses. In contrast, halothane (< or = approximately 17 mM), which acts on TREK-1 and TASK-1 channels, blocked acid taste responses. Agents diagnostic for other 2-pore domain and voltage-gated potassium channels (anandamide, 10 microM; Gd(3+), 1 mM; arachidonic acid, 100 microM; quinidine, 200 microM; quinine, 100 mM; 4-AP, 10 mM; and TEA, 1 mM) did not affect acid responses. The expression of 2-pore domain channels and our pharmacological characterization suggest that a matrix of ion channels, including one or more acid-sensitive 2-pore domain K channels, could play a role in sour taste transduction. However, our results do not unambiguously identify any one channel as the acid taste transducer.
据推测,酸味是由细胞内酸化引起的,细胞内酸化会调节味觉受体细胞中的一个或多个酸敏感离子通道。此类通道的具体身份仍不确定。钾通道通过调节味觉细胞的兴奋性,是酸传感器的候选者。几个双孔结构域钾渗漏电导通道(K(2)P家族)对细胞内酸化敏感。我们使用逆转录聚合酶链反应(RT-PCR)检测了它们在小鼠轮廓乳头和叶状乳头味蕾中的表达,并检测到了TWIK-1和-2、TREK-1和-2以及TASK-1。其中,相对于周围的非感觉上皮细胞,TWIK-1和TASK-1在味觉细胞中优先表达。未检测到相关的TRESK通道,而酸不敏感的TASK-2通道则被检测到。使用pH、Ca(2+)和电压敏感染料的共聚焦成像,我们测试了对这些通道具有诊断性的药物制剂。对TREK-1和-2通道具有选择性的利鲁唑(500 microM)增强了酸味反应。相比之下,作用于TREK-1和TASK-1通道的氟烷(≤约17 mM)则阻断了酸味反应。对其他双孔结构域和电压门控钾通道具有诊断性的药物制剂(花生四烯酸乙醇胺,10 microM;钆离子,1 mM;花生四烯酸,100 microM;奎尼丁,200 microM;奎宁,100 mM;4-氨基吡啶,10 mM;以及四乙铵,1 mM)并未影响酸味反应。双孔结构域通道的表达以及我们的药理学特征表明离子通道矩阵,包括一个或多个酸敏感的双孔结构域钾通道,可能在酸味转导中发挥作用。然而,我们的结果并未明确确定任何一个通道就是酸味传感器。