Abramowitz Joel, Birnbaumer Lutz
Transmembrane Signaling Group, Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
FASEB J. 2009 Feb;23(2):297-328. doi: 10.1096/fj.08-119495. Epub 2008 Oct 21.
The existence of a mammalian family of TRPC ion channels, direct homologues of TRP, the visual transduction channel of flies, was discovered during 1995-1996 as a consequence of research into the mechanism by which the stimulation of the receptor-Gq-phospholipase Cbeta signaling pathway leads to sustained increases in intracellular calcium. Mammalian TRPs, TRPCs, turned out to be nonselective, calcium-permeable cation channels, which cause both a collapse of the cell's membrane potential and entry of calcium. The family comprises 7 members and is widely expressed. Many cells and tissues express between 3 and 4 of the 7 TRPCs. Despite their recent discovery, a wealth of information has accumulated, showing that TRPCs have widespread roles in almost all cells studied, including cells from excitable and nonexcitable tissues, such as the nervous and cardiovascular systems, the kidney and the liver, and cells from endothelia, epithelia, and the bone marrow compartment. Disruption of TRPC function is at the root of some familial diseases. More often, TRPCs are contributing risk factors in complex diseases. The present article reviews what has been uncovered about physiological roles of mammalian TRPC channels since the time of their discovery. This analysis reveals TRPCs as major and unsuspected gates of Ca(2+) entry that contribute, depending on context, to activation of transcription factors, apoptosis, vascular contractility, platelet activation, and cardiac hypertrophy, as well as to normal and abnormal cell proliferation. TRPCs emerge as targets for a thus far nonexistent field of pharmacological intervention that may ameliorate complex diseases.
1995年至1996年期间，在研究受体-Gq-磷脂酶Cβ信号通路的刺激导致细胞内钙持续增加的机制时，发现了哺乳动物的TRPC离子通道家族，它是果蝇视觉转导通道TRP的直接同源物。哺乳动物的TRP，即TRPC，原来是非选择性的、钙可渗透的阳离子通道，它会导致细胞膜电位崩溃和钙进入。该家族由7个成员组成，广泛表达。许多细胞和组织表达7种TRPC中的3至4种。尽管它们是最近才被发现的，但已经积累了大量信息，表明TRPC在几乎所有研究的细胞中都有广泛作用，包括来自可兴奋和不可兴奋组织的细胞，如神经和心血管系统、肾脏和肝脏的细胞，以及内皮细胞、上皮细胞和骨髓区室的细胞。TRPC功能的破坏是一些家族性疾病的根源。更常见的是，TRPC是复杂疾病中的风险因素。本文回顾了自发现以来关于哺乳动物TRPC通道生理作用的研究成果。这一分析表明，TRPC是Ca(2+)进入的主要且未被怀疑的通道，根据具体情况，它有助于激活转录因子、诱导细胞凋亡、调节血管收缩、促进血小板活化和导致心脏肥大，以及影响正常和异常的细胞增殖。TRPC成为一个迄今为止不存在的药理学干预领域的靶点，该领域可能改善复杂疾病。
