The Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Cardiovasc Transl Res. 2010 Oct;3(5):516-24. doi: 10.1007/s12265-010-9208-4. Epub 2010 Jul 22.
Transient receptor potential channels are a large superfamily of non-selective and non-voltage-gated ion channels that convey signaling information linked to a broad range of sensory inputs. In the cardiovascular system, the canonical transient receptor potential (TRPC) family has been particularly found to play a role in vascular and cardiac disease, responding to neurohormonal and mechanical load stimulation. TRPC1, TRPC3, and TRPC6 are often upregulated in models of cardiovascular disease, and their inhibition ameliorates the associated pathophysiology. Studies in gene deletion models and overexpression models of wild-type and dominant-negative proteins supports a direct role of these channels, which likely act together as heterotetramers to influence signaling. Recent evidence has further revealed the importance of protein kinase G phosphorylation as a mechanism to suppress TRPC6 channel current and dependent signaling in vascular and cardiac myocytes. This suggests a novel mechanism underlying benefits of drugs such as sildenafil, a phosphodiesterase type 5 inhibitor, nitrates, and atrial natriuretic peptides. This review describes new evidence supporting a pathophysiologic role of these three TRPC channels, and the potential utility of inhibition strategies to treat cardiovascular disease.
瞬时受体电位通道是一个庞大的非选择性和非电压门控离子通道超家族，传递与广泛的感觉输入相关的信号信息。在心血管系统中，经典的瞬时受体电位（TRPC）家族已被特别发现与血管和心脏疾病有关，对神经激素和机械负荷刺激作出反应。在心血管疾病的模型中，TRPC1、TRPC3 和 TRPC6 经常上调，其抑制作用改善了相关的病理生理学。基因缺失模型和野生型和显性负性蛋白的过表达模型的研究支持这些通道的直接作用，这些通道可能作为异四聚体一起作用，影响信号。最近的证据进一步揭示了蛋白激酶 G 磷酸化作为抑制血管和心肌细胞中 TRPC6 通道电流和依赖信号的机制的重要性。这表明了西地那非（一种磷酸二酯酶 5 抑制剂）、硝酸盐和心钠肽等药物的益处的一个新的机制。本综述描述了支持这三个 TRPC 通道在病理生理学中的作用的新证据，以及抑制策略治疗心血管疾病的潜在效用。
