Riccio Antonio, Medhurst Andrew D, Mattei Cesar, Kelsell Rosemary E, Calver Andrew R, Randall Andrew D, Benham Christopher D, Pangalos Menelas N
Neurology and GI Centre of Excellence for Drug Discovery, New Frontiers Science Park, Harlow, Essex CM19 5AW, UK.
Brain Res Mol Brain Res. 2002 Dec 30;109(1-2):95-104. doi: 10.1016/s0169-328x(02)00527-2.
The mammalian homologues of the Drosophila transient receptor potential (TRP) channel are plasma membrane proteins involved in the regulation of cellular Ca(2+) influx. These ion channels can be activated subsequent to either depletion of Ca(2+) from internal stores or through receptor-mediated processes. The mRNA expression patterns of several individual mammalian short transient receptor potential channels (TRPCs) have been described. Cross-comparisons between these data, however, are at best difficult predominantly due to the non-quantitative methods used. Furthermore there is limited data on the expression of TRPC family members in human tissues. In the present study we used a single technique, namely TaqMan real-time quantitative RT-PCR, to investigate the mRNA distribution of human TRPC1, TRPC3, TRPC4, TRPC5, TRPC6 and TRPC7 (hTRPCs) in discrete human brain areas, peripheral tissues as well as a panel of cell-lines. All hTRPCs studied were widely expressed within CNS and significant peripheral expression was often observed. Despite this, each channel exhibited a distinctive hallmark distribution profile. hTRPC1 was widely expressed in CNS and peripheral tissues, whereas hTRPC3 and hTRPC5 were predominantly expressed in tissues of CNS. hTRPC4 mRNA was detected in CNS and certain peripheral tissues such as bone, heart and prostate. hTRPC6 was homogeneously expressed throughout the CNS and peripheral tissues with the highest levels in placenta and lung. hTRPC7 mRNA was also broadly expressed in CNS as well as some peripheral tissues. The pattern of expression of the TRPCs was quite different in the various cell lines examined. TRPC3 and TRPC6 were selectively present in HEK-293 cells whilst TRPC1 was broadly distributed in the cell lines analyzed. In contrast TRPC4 and TRPC5 mRNAs were predominantly expressed in HK-2 and HEK-293 cell lines respectively. TRPC7 was selectively expressed in COS-1, COS-7 and HK-2 cell lines. These results show tissue- and cell-specific co-expression of multiple TRPC forms indicating widespread potential for formation of heteromeric channels. These data will be useful in the complex task of relating channel subunit composition to function in native cells.
果蝇瞬时受体电位（TRP）通道的哺乳动物同源物是参与调节细胞钙（Ca2+）内流的质膜蛋白。这些离子通道可在细胞内钙库中的钙（Ca2+）耗尽后或通过受体介导的过程被激活。已经描述了几种单个哺乳动物短瞬时受体电位通道（TRPC）的mRNA表达模式。然而，由于所使用的非定量方法，这些数据之间的交叉比较充其量是困难的。此外，关于TRPC家族成员在人体组织中的表达数据有限。在本研究中，我们使用单一技术，即TaqMan实时定量RT-PCR，来研究人TRPC1、TRPC3、TRPC4、TRPC5、TRPC6和TRPC7（hTRPCs）在离散的人脑区域、外周组织以及一组细胞系中的mRNA分布。所研究的所有hTRPCs在中枢神经系统中广泛表达，并且经常观察到显著的外周表达。尽管如此，但每个通道都表现出独特的标志性分布特征。hTRPC1在中枢神经系统和外周组织中广泛表达，而hTRPC3和hTRPC5主要在中枢神经系统组织中表达。在中枢神经系统和某些外周组织如骨、心脏和前列腺中检测到hTRPC4 mRNA。hTRPC6在整个中枢神经系统和外周组织中均匀表达，在胎盘和肺中表达水平最高。hTRPC7 mRNA在中枢神经系统以及一些外周组织中也广泛表达。在所检测的各种细胞系中，TRPCs的表达模式差异很大。TRPC3和TRPC6选择性存在于HEK-293细胞中，而TRPC1广泛分布在所分析的细胞系中。相反，TRPC4和TRPC5 mRNA分别主要在HK-2和HEK-293细胞系中表达。TRPC7选择性表达于COS-1、COS-7和HK-2细胞系中。这些结果表明多种TRPC形式在组织和细胞中特异性共表达，这表明形成异源通道的可能性广泛。这些数据对于将通道亚基组成与天然细胞功能相关联的复杂任务将是有用的。
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